{"paper_id":"abdf2df8-54da-47fe-a5c8-269a4f193736","body_text":"The authors state that there are no conflicts of interest to disclose.\nG protein‐coupled receptors (GPCRs) are the largest class of membrane proteins in the human genome. The term \"7TM receptor\" is commonly used interchangeably with \"GPCR\", although there are some receptors with seven transmembrane domains that do not signal through G proteins. GPCRs share a common architecture, each consisting of a single polypeptide with an extracellular N‐terminus, an intracellular C‐terminus and seven hydrophobic transmembrane domains (TM1‐TM7) linked by three extracellular loops (ECL1‐ECL3) and three intracellular loops (ICL1‐ICL3). About 800 GPCRs have been identified in man, of which about half have sensory functions, mediating olfaction (˜400), taste (33), light perception (10) and pheromone signalling (5) [ http://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlus ]. The remaining 350 non‐sensory GPCRs mediate signalling by ligands that range in size from small molecules to peptides to large proteins; they are the targets for the majority of drugs in clinical usage [ http://www.ncbi.nlm.nih.gov/pubmed/17139284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24016212?dopt=AbstractPlus ], although only a minority of these receptors are exploited therapeutically. The first classification scheme to be proposed for GPCRs [ http://www.ncbi.nlm.nih.gov/pubmed/8081729?dopt=AbstractPlus ] divided them, on the basic of sequence homology, into six classes. These classes and their prototype members were as follows:  Class A  (rhodopsin‐like),  Class B  (secretin receptor family),  Class C  (metabotropic glutamate),  Class D  (fungal mating pheromone receptors),  Class E  (cyclic AMP receptors) and  Class F  (frizzled/smoothened). Of these, classes D and E are not found in vertebrates. An alternative classification scheme \"GRAFS\" [ http://www.ncbi.nlm.nih.gov/pubmed/15862553?dopt=AbstractPlus ] divides vertebrate GPCRs into five classes, overlapping with the A‐F nomenclature,  viz :\nGlutamate family  ( http://www.guidetopharmacology.org/GRAC/GPCRListForward?class=C ), which includes metabotropic glutamate receptors, a calcium‐sensing receptor and GABA B  receptors, as well as three taste type 1 receptors and a family of pheromone receptors (V2 receptors) that are abundant in rodents but absent in man [ http://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlus ].\nRhodopsin family  ( http://www.guidetopharmacology.org/GRAC/GPCRListForward?class=A ), which includes receptors for a wide variety of small molecules, neurotransmitters, peptides and hormones, together with olfactory receptors, visual pigments, taste type 2 receptors and five pheromone receptors (V1 receptors).\nhttp://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Adhesion  GPCRs are phylogenetically related to class B receptors, from which they differ by possessing large extracellular N‐termini that are autoproteolytically cleaved from their 7TM domains at a conserved \"GPCR proteolysis site\" (GPS) which lies within a much larger (320 residue) \"GPCR autoproteolysis‐inducing\" (GAIN) domain, an evolutionary ancient mofif also found in polycystic kidney disease 1 (PKD1)‐like proteins, which has been suggested to be both required and sufficient for autoproteolysis [ http://www.ncbi.nlm.nih.gov/pubmed/23850273?dopt=AbstractPlus ].\nhttp://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Frizzled  consists of 10 Frizzled proteins (FZD(1‐10)) and Smoothened (SMO). The FZDs are activated by secreted lipoglycoproteins of the WNT family, whereas SMO is indirectly activated by the Hedgehog (HH) family of proteins acting on the transmembrane protein Patched (PTCH).\nSecretin family,  encoded by 15 genes in humans. The ligands for receptors in this family are polypeptide hormones of 27‐141 amino acid residues; nine of the mammalian receptors respond to ligands that are structurally related to one another (glucagon, glucagon‐like peptides (GLP‐1, GLP‐2), glucose‐dependent insulinotropic polypeptide (GIP), secretin, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase‐activating polypeptide (PACAP) and growth‐hormone‐releasing hormone (GHRH)) [ http://www.ncbi.nlm.nih.gov/pubmed/11790261?dopt=AbstractPlus ].\nFamily \n \n Class A \n \n Class B (Secretin) \n \n Class C (Glutamate) \n \n Adhesion \n \n Frizzled \n \n Receptors with known ligands \n 197 15 12 0 11 \n Orphans \n 87 (54) a \n ‐ 8 (1) a \n 26 (6) a \n 0 \n Sensory (olfaction) \n 390 b,c \n ‐ ‐ ‐ ‐ \n Sensory (vision) \n 10 d  opsins ‐ ‐ ‐ ‐ \n Sensory (taste) \n 30 c  taste 2 ‐ 3 c  taste 1 ‐ ‐ \n Sensory (pheromone) \n 5 c  vomeronasal 1 ‐ ‐ ‐ ‐ \n Total \n 719 15 22 33 11\na Numbers in brackets refer to orphan receptors for which an endogenous ligand has been proposed in at least one publication, see [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ];  b [ http://www.ncbi.nlm.nih.gov/pubmed/19129093?dopt=AbstractPlus ];  c [ http://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlus ];  d [ http://www.ncbi.nlm.nih.gov/pubmed/15774036?dopt=AbstractPlus ].\nMuch of our current understanding of the structure and function of GPCRs is the result of pioneering work on the visual pigment rhodopsin and on the β 2  adrenoceptor, the latter culminating in the award of the 2012 Nobel Prize in chemistry to Robert Lefkowitz and Brian Kobilka [ http://www.ncbi.nlm.nih.gov/pubmed/23650120?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23650015?dopt=AbstractPlus ].\nBelow is a curated list of pseudogenes that in humans are non‐coding for receptor protein. In some cases these have a shared ancestry with genes that encode functional receptors in rats and mice.\nhttps://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19240 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16341 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4529 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16291 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7959 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4513 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:31924 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:31925 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19103 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19106 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19107 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20615 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20640 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20641 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20642 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:43898 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:43905 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20616 . A more detailed listing containg further information can be viewed  http://www.guidetopharmacology.org/GRAC//DATA/GPCR_pseudogenes.xlsx .\nOlfactory receptors are also seven‐transmembrane spanning G protein‐coupled receptors, responsible for the detection of odorants. These are not currently included as they are not yet associated with extensive pharmacological data but are curated in the following databases: The gene list of olfactory receptors at  https://www.genenames.org/cgi‐bin/genefamilies/set/141 , and curated by  https://genome.weizmann.ac.il/horde/  and  https://senselab.med.yale.edu/ordb/ .\nKenakin T. (2018) Is the Quest for Signaling Bias Worth the Effort?  Mol. Pharmacol. \n 93 : 266‐269 [ https://www.ncbi.nlm.nih.gov/pubmed/29348268?dopt=AbstractPlus ]\nMichel MC  et al . (2018) Biased Agonism in Drug Discovery‐Is It Too Soon to Choose a Path?  Mol. Pharmacol. \n 93 : 259‐265 [ https://www.ncbi.nlm.nih.gov/pubmed/29326242?dopt=AbstractPlus ]\nRoth BL  et al . (2017) Discovery of new GPCR ligands to illuminate new biology.  Nat. Chem. Biol. \n 13 : 1143‐1151 [ https://www.ncbi.nlm.nih.gov/pubmed/29045379?dopt=AbstractPlus ]\nSriram K  et al . (2018) G Protein‐Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?  Mol. Pharmacol. \n 93 : 251‐258 [ https://www.ncbi.nlm.nih.gov/pubmed/29298813?dopt=AbstractPlus ]\nS23 Orphan and other 7TM receptors\nS24 Class A Orphans\n–  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=706\nS33 Class C Orphans\n– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=975\nS33 Taste 1 receptors\nS34 Taste 2 receptors\nS35 Other 7TM proteins\nS36 5‐Hydroxytryptamine receptors\nS39 Acetylcholine receptors (muscarinic)\nS41 Adenosine receptors\nS42 Adhesion Class GPCRs\nS45 Adrenoceptors\nS48 Angiotensin receptors\nS50 Apelin receptor\nS51 Bile acid receptor\nS51 Bombesin receptors\nS53 Bradykinin receptors\nS54 Calcitonin receptors\nS56 Calcium‐sensing receptor\nS57 Cannabinoid receptors\nS58 Chemerin receptors\nS59 Chemokine receptors\nS63 Cholecystokinin receptors\nS64 Class Frizzled GPCRs\nS67 Complement peptide receptors\nS68 Corticotropin‐releasing factor receptors\nS69 Dopamine receptors\nS71 Endothelin receptors\nS72 G protein‐coupled estrogen receptor\nS73 Formylpeptide receptors\nS74 Free fatty acid receptors\nS76 GABA B  receptors\nS78 Galanin receptors\nS79 Ghrelin receptor\nS80 Glucagon receptor family\nS81 Glycoprotein hormone receptors\nS82 Gonadotrophin‐releasing hormone receptors\nS83 GPR18, GPR55 and GPR119\nS84 Histamine receptors\nS86 Hydroxycarboxylic acid receptors\nS87 Kisspeptin receptor\nS88 Leukotriene receptors\nS89 Lysophospholipid (LPA) receptors\nS90 Lysophospholipid (S1P) receptors\nS92 Melanin‐concentrating hormone receptors\nS93 Melanocortin receptors\nS94 Melatonin receptors\nS95 Metabotropic glutamate receptors\nS97 Motilin receptor\nS98 Neuromedin U receptors\nS99 Neuropeptide FF/neuropeptide AF receptors\nS100 Neuropeptide S receptor\nS101 Neuropeptide W/neuropeptide B receptors\nS102 Neuropeptide Y receptors\nS103 Neurotensin receptors\nS104 Opioid receptors\nS106 Orexin receptors\nS107 Oxoglutarate receptor\nS108 P2Y receptors\nS110 Parathyroid hormone receptors\nS111 Platelet‐activating factor receptor\nS112 Prokineticin receptors\nS113 Prolactin‐releasing peptide receptor\nS114 Prostanoid receptors\nS116 Proteinase‐activated receptors\nS117 QRFP receptor\nS118 Relaxin family peptide receptors\nS120 Somatostatin receptors\nS121 Succinate receptor\nS122 Tachykinin receptors\nS123 Thyrotropin‐releasing hormone receptors\nS124 Trace amine receptor\nS125 Urotensin receptor\nS126 Vasopressin and oxytocin receptors\nS127 VIP and PACAP receptors\nThis set contains ’orphan’ G protein coupled receptors where the endogenous ligand(s) is not known, and other 7TM receptors.\nTable 1 lists a number of putative GPCRs identified by  NC‐IUPHAR [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. The GPCRs in Table 1 are all Class A, rhodopsin‐like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as‐yet unidentified endogenous ligands.\nClass A orphan GPCRs with putative endogenous ligands\n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=83 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=84 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=85 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=86 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=87 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=88 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=91 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=93 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=96 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=98 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=101 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=102 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=103 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=105 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=107 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=112 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=113 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=114 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=115 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=120 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=122 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=123 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=128 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=135 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=141 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=81 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=147 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=148 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=149 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=150 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=152 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=156 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=157 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=165 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=167\nIn addition the orphan receptors  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=89 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=109  and  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=126  which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together ( http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=114 ).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=83 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=84 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=85 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4484 ,  http://www.uniprot.org/uniprot/P46089 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4497 ,  http://www.uniprot.org/uniprot/P46093 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4515 ,  http://www.uniprot.org/uniprot/P46095 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7802  [ http://www.ncbi.nlm.nih.gov/pubmed/24633425?dopt=AbstractPlus ] – – Endogenous ligands – Protons – Comments \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  was reported to be an endogenous agonist [ http://www.ncbi.nlm.nih.gov/pubmed/12220620?dopt=AbstractPlus ], but this finding was not replicated in subsequent studies [ http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. Reported to activate adenylyl cyclase constitutively through G s  [ http://www.ncbi.nlm.nih.gov/pubmed/7639700?dopt=AbstractPlus ]. Gene disruption results in premature ovarian ageing [ http://www.ncbi.nlm.nih.gov/pubmed/15956199?dopt=AbstractPlus ], reduced β‐amyloid deposition [ http://www.ncbi.nlm.nih.gov/pubmed/19213921?dopt=AbstractPlus ] and hypersensitivity to thermal pain [ http://www.ncbi.nlm.nih.gov/pubmed/21352831?dopt=AbstractPlus ] in mice. First small molecule inverse agonist [ http://www.ncbi.nlm.nih.gov/pubmed/25442311?dopt=AbstractPlus ] and agonists identified [ http://www.ncbi.nlm.nih.gov/pubmed/24633425?dopt=AbstractPlus ] An initial report suggesting activation by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2508  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4032  [ http://www.ncbi.nlm.nih.gov/pubmed/11535583?dopt=AbstractPlus ] has been retracted [ http://www.ncbi.nlm.nih.gov/pubmed/16498716?dopt=AbstractPlus ]. GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton‐sensing receptors detecting acidic pH [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17118800?dopt=AbstractPlus ]. Gene disruption is associated with increased perinatal mortality and impaired vascular proliferation [ http://www.ncbi.nlm.nih.gov/pubmed/17145776?dopt=AbstractPlus ]. Negative allosteric modulators of GPR4 have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/26070068?dopt=AbstractPlus ]. An initial report that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  (S1P) was a high‐affinity ligand (EC 50  value of 39nM) [ http://www.ncbi.nlm.nih.gov/pubmed/14592418?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12220620?dopt=AbstractPlus ] was not repeated in arrestin‐based assays [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. Reported to activate adenylyl cyclase constitutively through G s  and to be located intracellularly [ http://www.ncbi.nlm.nih.gov/pubmed/19059244?dopt=AbstractPlus ]. GPR6‐deficient mice showed reduced striatal cyclic AMP production  in vitro  and selected alterations in instrumental conditioning  in vivo . [ http://www.ncbi.nlm.nih.gov/pubmed/17934457?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=86 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=87 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=88 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4466 ,  http://www.uniprot.org/uniprot/P47775 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4469 ,  http://www.uniprot.org/uniprot/P49685 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4471 ,  http://www.uniprot.org/uniprot/Q13304 \n Endogenous agonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1783  [ http://www.ncbi.nlm.nih.gov/pubmed/20148890?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354  [ http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1782  [ http://www.ncbi.nlm.nih.gov/pubmed/20148890?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749  [ http://www.ncbi.nlm.nih.gov/pubmed/20148890?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353 [ http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ] Comments Reports that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  is a ligand of GPR12 [ http://www.ncbi.nlm.nih.gov/pubmed/12574419?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12220620?dopt=AbstractPlus ] have not been replicated in arrestin‐based assays [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. Gene disruption results in dyslipidemia and obesity [ http://www.ncbi.nlm.nih.gov/pubmed/16887097?dopt=AbstractPlus ]. Reported to act as a co‐receptor for HIV [ http://www.ncbi.nlm.nih.gov/pubmed/9405683?dopt=AbstractPlus ]. In an infection‐induced colitis model,  Gpr15  knockout mice were more prone to tissue damage and inflammatory cytokine expression [ http://www.ncbi.nlm.nih.gov/pubmed/23661644?dopt=AbstractPlus ]. Reported to be a dual leukotriene and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ]. Another group instead proposed that GPR17 functions as a negative regulator of the CysLT 1  receptor response to leukotriene D 4  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353 ). For further discussion, see [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. Reported to antagonize CysLT 1  receptor signalling  in vivo  and  in vitro  [ http://www.ncbi.nlm.nih.gov/pubmed/19561298?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=90 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=91 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=92 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=93 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=95 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=96 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=97 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4473 ,  http://www.uniprot.org/uniprot/Q15760 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4475 ,  http://www.uniprot.org/uniprot/Q99678 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4476 ,  http://www.uniprot.org/uniprot/Q99679 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4477 ,  http://www.uniprot.org/uniprot/Q99680 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4480 ,  http://www.uniprot.org/uniprot/O00155 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4481 ,  http://www.uniprot.org/uniprot/Q8NDV2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4482 ,  http://www.uniprot.org/uniprot/Q9NS67 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9573  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24838 ,  http://www.uniprot.org/uniprot/Q6UWT2 ) [ http://www.ncbi.nlm.nih.gov/pubmed/28476646?dopt=AbstractPlus ] – – – – – – Comments – Reported to inhibit adenylyl cyclase constitutively through G i/o  [ http://www.ncbi.nlm.nih.gov/pubmed/18347022?dopt=AbstractPlus ]. GPR20 deficient mice exhibit hyperactivity characterised by increased total distance travelled in an open field test [ 230 ]. \n Gpr21  knockout mice were resistant to diet‐induced obesity, exhibiting an increase in glucose tolerance and insulin sensitivity, as well as a modest lean phenotype [ http://www.ncbi.nlm.nih.gov/pubmed/22653059?dopt=AbstractPlus ]. Gene disruption results in increased severity of functional decompensation following aortic banding [ http://www.ncbi.nlm.nih.gov/pubmed/18539757?dopt=AbstractPlus ]. Identified as a susceptibility locus for osteoarthritis [ http://www.ncbi.nlm.nih.gov/pubmed/21068099?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20112360?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20090528?dopt=AbstractPlus ]. – Has been reported to activate adenylyl cyclase constitutively through G s  [ http://www.ncbi.nlm.nih.gov/pubmed/17363172?dopt=AbstractPlus ].  Gpr26  knockout mice show increased levels of anxiety and depression‐like behaviours [ http://www.ncbi.nlm.nih.gov/pubmed/21924326?dopt=AbstractPlus ]. Knockdown of Gpr27 reduces endogenous mouse insulin promotor activity and glucose‐stimulated insulin secretion [ http://www.ncbi.nlm.nih.gov/pubmed/22253604?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=98 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=99 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=100 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=101 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4486 ,  http://www.uniprot.org/uniprot/O00270 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4487 ,  http://www.uniprot.org/uniprot/O75388 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4489 ,  http://www.uniprot.org/uniprot/Q49SQ1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4490 ,  http://www.uniprot.org/uniprot/Q9UPC5 \n Potency order of endogenous ligands – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034 \n – – Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3404  [ http://www.ncbi.nlm.nih.gov/pubmed/21712392?dopt=AbstractPlus ] – Mouse \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034  [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4064  [ http://www.ncbi.nlm.nih.gov/pubmed/22343749?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16460680?dopt=AbstractPlus ] Labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4356  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ] – – Comments See [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] for discussion of pairing. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  has been demonstrated to activate GPR32 in two publications [ http://www.ncbi.nlm.nih.gov/pubmed/22538616?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ]. The pairing was not replicated in a recent study based on arrestin recruitment [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ].  GPR32  is a pseudogene in mice and rats. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. \n GPR33  is a pseudogene in most individuals, containing a premature stop codon within the coding sequence of the second intracellular loop [ http://www.ncbi.nlm.nih.gov/pubmed/15987686?dopt=AbstractPlus ]. Lysophosphatidylserine has been reported to be a ligand of GPR34 in several publications, but the pairing was not replicated in a recent study based on arrestin recruitment [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]. Fails to respond to a variety of lipid‐derived agents [ http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. Gene disruption results in an enhanced immune response [ http://www.ncbi.nlm.nih.gov/pubmed/21097509?dopt=AbstractPlus ]. Characterization of agonists at this receptor is discussed in [ http://www.ncbi.nlm.nih.gov/pubmed/25970039?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=102 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=103 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4492 ,  http://www.uniprot.org/uniprot/Q9HC97 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4494 ,  http://www.uniprot.org/uniprot/O15354 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2936  [ http://www.ncbi.nlm.nih.gov/pubmed/20361937?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2918  [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16754668?dopt=AbstractPlus ] – Agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2496  [ http://www.ncbi.nlm.nih.gov/pubmed/16443751?dopt=AbstractPlus ] Comments Several studies have shown that kynurenic acid is an agonist of GPR35 but it remains controversial whether the proposed endogenous ligand reaches sufficient tissue concentrations to activate the receptor [ http://www.ncbi.nlm.nih.gov/pubmed/18235993?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2936  has also been proposed as an endogenous ligand [ http://www.ncbi.nlm.nih.gov/pubmed/20361937?dopt=AbstractPlus ] but these results were not replicated in an arrestin assay [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]. The phosphodiesterase inhibitor  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2919  [ http://www.ncbi.nlm.nih.gov/pubmed/16934253?dopt=AbstractPlus ] has become widely used as a surrogate agonist to investigate GPR35 pharmacology and signalling [ http://www.ncbi.nlm.nih.gov/pubmed/16934253?dopt=AbstractPlus ]. GPR35 is also activated by the pharmaceutical adjunct  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2920  [ http://www.ncbi.nlm.nih.gov/pubmed/20826425?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/25805994?dopt=AbstractPlus ]. Reported to associate and regulate the dopamine transporter [ http://www.ncbi.nlm.nih.gov/pubmed/17519329?dopt=AbstractPlus ] and to be a substrate for parkin [ http://www.ncbi.nlm.nih.gov/pubmed/19398891?dopt=AbstractPlus ]. Gene disruption results in altered striatal signalling [ http://www.ncbi.nlm.nih.gov/pubmed/21372109?dopt=AbstractPlus ]. The peptides prosaptide and prosaposin are proposed as endogenous ligands for GPR37 and GPR37L1 [ http://www.ncbi.nlm.nih.gov/pubmed/23690594?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=104 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=105 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=106 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=107 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14923 ,  http://www.uniprot.org/uniprot/O60883 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4496 ,  http://www.uniprot.org/uniprot/O43194 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4503 ,  http://www.uniprot.org/uniprot/Q9Y5Y3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4506 ,  http://www.uniprot.org/uniprot/Q13585 \n Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=566  [ http://www.ncbi.nlm.nih.gov/pubmed/16959833?dopt=AbstractPlus ] – – Comments The peptides prosaptide and prosaposin are proposed as endogenous ligands for GPR37 and GPR37L1 [ http://www.ncbi.nlm.nih.gov/pubmed/23690594?dopt=AbstractPlus ]. Zn 2+  has been reported to be a potent and efficacious agonist of human, mouse and rat GPR39 [ http://www.ncbi.nlm.nih.gov/pubmed/17214962?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5336  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ), a fragment from the ghrelin precursor, was reported initially as an endogenous ligand, but subsequent studies failed to reproduce these findings.  GPR39  has been reported to be down‐regulated in adipose tissue in obesity‐related diabetes [ http://www.ncbi.nlm.nih.gov/pubmed/17371481?dopt=AbstractPlus ]. Gene disruption results in obesity and altered adipocyte metabolism [ http://www.ncbi.nlm.nih.gov/pubmed/21784784?dopt=AbstractPlus ]. Reviewed in [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. – GPR50 is structurally related to MT 1  and MT 2  melatonin receptors, with which it heterodimerises constitutively and specifically [ http://www.ncbi.nlm.nih.gov/pubmed/16778767?dopt=AbstractPlus ].  Gpr50  knockout mice display abnormal thermoregulation and are much more likely than wild‐type mice to enter fasting‐induced torpor [ http://www.ncbi.nlm.nih.gov/pubmed/22197240?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=108 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=110 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=111 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=112 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4508 ,  http://www.uniprot.org/uniprot/Q9Y2T5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13300 ,  http://www.uniprot.org/uniprot/Q9BZJ8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13301 ,  http://www.uniprot.org/uniprot/Q9BZJ7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13302 ,  http://www.uniprot.org/uniprot/Q9BZJ6 \n Comments First small molecule agonist reported [ http://www.ncbi.nlm.nih.gov/pubmed/24884590?dopt=AbstractPlus ]. GPR61 deficient mice exhibit obesity associated with hyperphagia [ http://www.ncbi.nlm.nih.gov/pubmed/21971119?dopt=AbstractPlus ]. Although no endogenous ligands have been identified, 5‐(nonyloxy)tryptamine has been reported to be a low affinity inverse agonist [ http://www.ncbi.nlm.nih.gov/pubmed/15173198?dopt=AbstractPlus ]. – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5512  have been reported to be low affinity agonists for GPR63 [ http://www.ncbi.nlm.nih.gov/pubmed/12618218?dopt=AbstractPlus ] but this finding was not replicated in an arrestin‐based assay [ http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=113 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=114 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4517 ,  http://www.uniprot.org/uniprot/Q8IYL9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4519 ,  http://www.uniprot.org/uniprot/Q15743 \n Endogenous ligands Protons Protons Allosteric modulators – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9155  (Positive) (p K \n B  5) [ http://www.ncbi.nlm.nih.gov/pubmed/26550826?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5884  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/26550826?dopt=AbstractPlus ] Comments GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton‐sensing receptors detecting acidic pH [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17118800?dopt=AbstractPlus ]. Reported to activate adenylyl cyclase; gene disruption leads to reduced eosinophilia in models of allergic airway disease [ http://www.ncbi.nlm.nih.gov/pubmed/19641187?dopt=AbstractPlus ]. GPR68 was previously identified as a receptor for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4032  (SPC) [ http://www.ncbi.nlm.nih.gov/pubmed/10806476?dopt=AbstractPlus ], but the original publication has been retracted [ http://www.ncbi.nlm.nih.gov/pubmed/16508674?dopt=AbstractPlus ]. GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton‐sensing receptors detecting acidic pH [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17118800?dopt=AbstractPlus ]. A family of 3,5‐disubstituted isoxazoles were identified as agonists of GPR68 [ http://www.ncbi.nlm.nih.gov/pubmed/22462679?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=115 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=116 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=117 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=118 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4526 ,  http://www.uniprot.org/uniprot/O95800 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4528 ,  http://www.uniprot.org/uniprot/Q96P69 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4529 , – \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4533 ,  http://www.uniprot.org/uniprot/Q96P67 \n Comments \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758 ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ) was reported to be an agonist of GPR75 [ http://www.ncbi.nlm.nih.gov/pubmed/17001303?dopt=AbstractPlus ], but the pairing could not be repeated in an arrestin assay [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]. GPR78 has been reported to be constitutively active, coupled to elevated cAMP production [ http://www.ncbi.nlm.nih.gov/pubmed/17363172?dopt=AbstractPlus ]. – Mice with  Gpr82  knockout have a lower body weight and body fat content associated with reduced food intake, decreased serum triglyceride levels, as well as higher insulin sensitivity and glucose tolerance [ http://www.ncbi.nlm.nih.gov/pubmed/22216272?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=119 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=120 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=121 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=122 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=123 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=125 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4523 ,  http://www.uniprot.org/uniprot/Q9NYM4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4535 ,  http://www.uniprot.org/uniprot/Q9NQS5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4536 ,  http://www.uniprot.org/uniprot/P60893 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4538 ,  http://www.uniprot.org/uniprot/Q9BY21 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4539 ,  http://www.uniprot.org/uniprot/Q9GZN0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14963 ,  http://www.uniprot.org/uniprot/Q96P66 \n Endogenous agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2906  [ http://www.ncbi.nlm.nih.gov/pubmed/18466763?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17905198?dopt=AbstractPlus ] – – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9139  {Mouse} [ http://www.ncbi.nlm.nih.gov/pubmed/27117253?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=566  [ http://www.ncbi.nlm.nih.gov/pubmed/23335960?dopt=AbstractPlus ] – Mouse \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5532  [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16966319?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5533 [ http://www.ncbi.nlm.nih.gov/pubmed/16966319?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5534 [ http://www.ncbi.nlm.nih.gov/pubmed/16966319?dopt=AbstractPlus ] – – – – Comments One isoform has been implicated in the induction of CD4(+) CD25(+) regulatory T cells (Tregs) during inflammatory immune responses [ http://www.ncbi.nlm.nih.gov/pubmed/20200545?dopt=AbstractPlus ]. The extracellular N‐terminal domain is reported as an intramolecular inverse agonist [ http://www.ncbi.nlm.nih.gov/pubmed/25516095?dopt=AbstractPlus ]. Medium chain free fatty acids with carbon chain lengths of 9‐14 activate GPR84 [ http://www.ncbi.nlm.nih.gov/pubmed/23449982?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16966319?dopt=AbstractPlus ]. A surrogate ligand for GPR84,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5846  has also been proposed [ http://www.ncbi.nlm.nih.gov/pubmed/23449982?dopt=AbstractPlus ]. See review [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] for discussion of classification. Mutational analysis and molecular modelling of GPR84 has been reported [ http://www.ncbi.nlm.nih.gov/pubmed/25425658?dopt=AbstractPlus ]. Proposed to regulate hippocampal neurogenesis in the adult, as well as neurogenesis‐dependent learning and memory [ http://www.ncbi.nlm.nih.gov/pubmed/22697179?dopt=AbstractPlus ]. – Gene disruption results in altered striatal signalling [ http://www.ncbi.nlm.nih.gov/pubmed/19796684?dopt=AbstractPlus ]. Small molecule agonists have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/25754495?dopt=AbstractPlus ]. Mutations in GPR101 have been linked to gigantism and acromegaly [ http://www.ncbi.nlm.nih.gov/pubmed/25470569?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=128 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=129 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=130 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=131 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=132 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=133 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17482 ,  http://www.uniprot.org/uniprot/Q9UNW8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19991 ,  http://www.uniprot.org/uniprot/Q8IZ08 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19995 ,  http://www.uniprot.org/uniprot/Q6DWJ6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19997 ,  http://www.uniprot.org/uniprot/Q7Z602 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20088 ,  http://www.uniprot.org/uniprot/Q7Z601 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:21718 ,  http://www.uniprot.org/uniprot/Q96CH1 \n Endogenous ligands Protons – – – – – Comments GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton‐sensing receptors detecting acidic pH [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17118800?dopt=AbstractPlus ]. Reported to respond to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2508  [ http://www.ncbi.nlm.nih.gov/pubmed/11474113?dopt=AbstractPlus ], but later retracted [ http://www.ncbi.nlm.nih.gov/pubmed/15653487?dopt=AbstractPlus ]. – Peptide agonists have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/24826842?dopt=AbstractPlus ]. – Small molecule agonists have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/24900747?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24900757?dopt=AbstractPlus ]. Yosten  et al . demonstrated inhibition of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6145  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6081 ,  http://www.uniprot.org/uniprot/P01308 )‐induced stimulation of cFos expression folllowing knockdown of GPR146 in KATO III cells, suggesting proinsulin C‐peptide as an endogenous ligand of the receptor [ http://www.ncbi.nlm.nih.gov/pubmed/23759446?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=134 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=135 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=136 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=137 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=138 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=139 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=140 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23623 ,  http://www.uniprot.org/uniprot/Q8TDV2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23627 ,  http://www.uniprot.org/uniprot/Q86SP6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23628 ,  http://www.uniprot.org/uniprot/Q8NGU9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23624 ,  http://www.uniprot.org/uniprot/Q8TDV0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23622 ,  http://www.uniprot.org/uniprot/Q8TDT2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23618 ,  http://www.uniprot.org/uniprot/Q6NV75 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23693 ,  http://www.uniprot.org/uniprot/Q9UJ42 \n Comments – \n Gpr149  knockout mice displayed increased fertility and enhanced ovulation, with increased levels of FSH receptor and cyclin D2 mRNA levels [ http://www.ncbi.nlm.nih.gov/pubmed/19887567?dopt=AbstractPlus ]. – GPR151 responded to galanin with an EC 50  value of 2  μ M, suggesting that the endogenous ligand shares structural features with  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15111018?dopt=AbstractPlus ]. – – – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=141 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=142 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=143 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=144 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23694 ,  http://www.uniprot.org/uniprot/Q8N6U8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16693 ,  http://www.uniprot.org/uniprot/Q16538 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30057 ,  http://www.uniprot.org/uniprot/O14626 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18186 ,  http://www.uniprot.org/uniprot/Q9NS66 \n Comments A C‐terminal truncation (deletion) mutation in Gpr161 causes congenital cataracts and neural tube defects in the vacuolated lens (vl) mouse mutant [ http://www.ncbi.nlm.nih.gov/pubmed/18250320?dopt=AbstractPlus ]. The mutated receptor is associated with cataract, spina bifida and white belly spot phenotypes in mice [ http://www.ncbi.nlm.nih.gov/pubmed/18796533?dopt=AbstractPlus ]. Gene disruption is associated with a failure of asymmetric embryonic development in zebrafish [ http://www.ncbi.nlm.nih.gov/pubmed/18755178?dopt=AbstractPlus ]. – GPR171 has been shown to be activated by the endogenous peptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6704  {Mouse}. This receptor‐peptide interaction is believed to be involved in regulating feeding and metabolism responses [ http://www.ncbi.nlm.nih.gov/pubmed/24043826?dopt=AbstractPlus ]. – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=145 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=637 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=146 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=81 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30245 ,  http://www.uniprot.org/uniprot/Q9BXC1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:32370 ,  http://www.uniprot.org/uniprot/Q14439 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13708 ,  http://www.uniprot.org/uniprot/O15218 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3128 ,  http://www.uniprot.org/uniprot/P32249 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4064  [ http://www.ncbi.nlm.nih.gov/pubmed/22983457?dopt=AbstractPlus ] – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4350  [ http://www.ncbi.nlm.nih.gov/pubmed/21796212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21796211?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4353 [ http://www.ncbi.nlm.nih.gov/pubmed/21796211?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4355 [ http://www.ncbi.nlm.nih.gov/pubmed/21796211?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4354 [ http://www.ncbi.nlm.nih.gov/pubmed/21796211?dopt=AbstractPlus ] Comments See [ http://www.ncbi.nlm.nih.gov/pubmed/25970039?dopt=AbstractPlus ] which discusses characterization of agonists at this receptor. – Rat GPR182 was first proposed as the adrenomedullin receptor [ http://www.ncbi.nlm.nih.gov/pubmed/7592696?dopt=AbstractPlus ]. However, it was later reported that rat and human GPR182 did not respond to adrenomedullin [ http://www.ncbi.nlm.nih.gov/pubmed/9535752?dopt=AbstractPlus ] and GPR182 is not currently considered to be a genuine adrenomedullin receptor [ http://www.ncbi.nlm.nih.gov/pubmed/21051558?dopt=AbstractPlus ]. Two independent publications have shown that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4350  is an agonist of GPR183 and have demonstrated by mass spectrometry that this oxysterol is present endogenously in tissues [ http://www.ncbi.nlm.nih.gov/pubmed/21796212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21796211?dopt=AbstractPlus ]. Gpr183‐deficient mice show a reduction in the early antibody response to a T‐dependent antigen. GPR183‐deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [ http://www.ncbi.nlm.nih.gov/pubmed/21844396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19597478?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=147 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=148 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=149 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13299 ,  http://www.uniprot.org/uniprot/Q9BXB1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4504 ,  http://www.uniprot.org/uniprot/O75473 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19719 ,  http://www.uniprot.org/uniprot/Q9HBX8 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3698  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28583 ,  http://www.uniprot.org/uniprot/Q6UXX9 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3697  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:21679 ,  http://www.uniprot.org/uniprot/Q2MKA7 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3699  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20866 ,  http://www.uniprot.org/uniprot/Q9BXY4 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3700  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16175 ,  http://www.uniprot.org/uniprot/Q2I0M5 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3698  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28583 ,  http://www.uniprot.org/uniprot/Q6UXX9 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3697  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:21679 ,  http://www.uniprot.org/uniprot/Q2MKA7 )  http://www.uniprot.org/uniprot/Q2MKA7 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3699  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20866 ,  http://www.uniprot.org/uniprot/Q9BXY4 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3700  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16175 ,  http://www.uniprot.org/uniprot/Q2I0M5 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3697  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:21679 ,  http://www.uniprot.org/uniprot/Q2MKA7 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3698  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28583 ,  http://www.uniprot.org/uniprot/Q6UXX9 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3699  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20866 ,  http://www.uniprot.org/uniprot/Q9BXY4 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3700  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16175 ,  http://www.uniprot.org/uniprot/Q2I0M5 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ] Comments LGR4 does not couple to heterotrimeric G proteins or recruit arrestins when stimulated by the R‐spondins, indicating a unique mechanism of action. R‐spondins bind to LGR4, which specifically associates with Frizzled and LDL receptor‐related proteins (LRPs) that are activated by the extracellular Wnt molecules and then trigger canonical Wnt signalling to increase gene expression [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22815884?dopt=AbstractPlus ]. Gene disruption leads to multiple developmental disorders [ http://www.ncbi.nlm.nih.gov/pubmed/18487371?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19605502?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18955481?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18424556?dopt=AbstractPlus ]. The four R‐spondins can bind to LGR4, LGR5, and LGR6, which specifically associate with Frizzled and LDL receptor‐related proteins (LRPs), proteins that are activated by extracellular Wnt molecules and which then trigger canonical Wnt signalling to increase gene expression [ http://www.ncbi.nlm.nih.gov/pubmed/21693646?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21727895?dopt=AbstractPlus ]. – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=150 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=151 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6899 ,  http://www.uniprot.org/uniprot/P04201 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13961 ,  http://www.uniprot.org/uniprot/P35410 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=582 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21670420?dopt=AbstractPlus ] – Mouse – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=152 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=153 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=154 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=155 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29626 ,  http://www.uniprot.org/uniprot/Q8TDS7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30694 ,  http://www.uniprot.org/uniprot/Q86SM8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24828 ,  http://www.uniprot.org/uniprot/Q96AM1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24829 ,  http://www.uniprot.org/uniprot/Q86SM5 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2365  [ http://www.ncbi.nlm.nih.gov/pubmed/15037633?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ] – – – Comments An endogenous peptide with a high degree of sequence similarity to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=582 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6065  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ), was shown to promote NO release in MRGPRD‐transfected cells. The binding of alamandine to MRGPRD to was shown to be blocked by D‐Pro 7 ‐angiotensin‐(1‐7),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2365  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=597  [ http://www.ncbi.nlm.nih.gov/pubmed/23446738?dopt=AbstractPlus ]. Genetic ablation of MRGPRD+ neurons of adult mice decreased behavioural sensitivity to mechanical stimuli but not to thermal stimuli [ http://www.ncbi.nlm.nih.gov/pubmed/19451647?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. MRGPRF has been reported to respond to stimulation by angiotensin metabolites [ http://www.ncbi.nlm.nih.gov/pubmed/18636314?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=156 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=157 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=158 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=159 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=164 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=165 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17962 ,  http://www.uniprot.org/uniprot/Q96LB2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17983 ,  http://www.uniprot.org/uniprot/Q96LB1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17980 ,  http://www.uniprot.org/uniprot/Q96LB0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17617 ,  http://www.uniprot.org/uniprot/Q96LA9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15524 ,  http://www.uniprot.org/uniprot/Q86VZ1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19906 ,  http://www.uniprot.org/uniprot/O00398 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4058  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15163697?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11850634?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4057  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15823563?dopt=AbstractPlus ] – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  [ http://www.ncbi.nlm.nih.gov/pubmed/18466763?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2906  [ http://www.ncbi.nlm.nih.gov/pubmed/18466763?dopt=AbstractPlus ] Agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2007  {Mouse, Rat} [ http://www.ncbi.nlm.nih.gov/pubmed/15823563?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28288109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12915402?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ] – – – – Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4056 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15823563?dopt=AbstractPlus ] – – – – Comments Reported to mediate the sensation of itch [ http://www.ncbi.nlm.nih.gov/pubmed/20004959?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21593341?dopt=AbstractPlus ]. Reports that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4058  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) was the most potent of a series of proenkephalin A‐derived peptides as an agonist of MRGPRX1 in assays of calcium mobilisation and radioligand binding [ http://www.ncbi.nlm.nih.gov/pubmed/11850634?dopt=AbstractPlus ] were replicated in an independent study using an arrestin recruitment assay [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. A diverse range of substances has been reported to be agonists of MRGPRX2, with cortistatin 14 the highest potency agonist in assays of calcium mobilisation [ http://www.ncbi.nlm.nih.gov/pubmed/12915402?dopt=AbstractPlus ], also confirmed in an independent study using an arrestin recruitment assay [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. – See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/24867890?dopt=AbstractPlus ]. – – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=167 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=168 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=169 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=170 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=171 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=172 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=173 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4514 ,  http://www.uniprot.org/uniprot/Q9P1P5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4513 ,  http://www.uniprot.org/uniprot/Q9P1P4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:31924 , – \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30236 ,  http://www.uniprot.org/uniprot/O14804 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20978 ,  http://www.uniprot.org/uniprot/Q96RI8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14964 ,  http://www.uniprot.org/uniprot/Q969N4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20977 ,  http://www.uniprot.org/uniprot/Q96RI9 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2144  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=125  [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ] – – – – – – Comments Probable pseudogene in 10–15% of Asians due to a polymorphism (rs8192646) producing a premature stop codon at amino acid 168 [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. \n TAAR3  is thought to be a pseudogene in man though functional in rodents [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. Pseudogene in man but functional in rodents [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. Trimethylamine is reported as an agonist [ http://www.ncbi.nlm.nih.gov/pubmed/23393561?dopt=AbstractPlus ] and 3‐iodothyronamine an inverse agonist [ http://www.ncbi.nlm.nih.gov/pubmed/25706283?dopt=AbstractPlus ]. – – \n TAAR9  appears to be functional in most individuals but has a polymorphic premature stop codon at amino acid 61 (rs2842899) with an allele frequency of 10–30% in different populations [ http://www.ncbi.nlm.nih.gov/pubmed/14559210?dopt=AbstractPlus ].\nMcNeil BD  et al . (2015) Identification of a mast‐cell‐specific receptor crucial for pseudo‐allergic drug reactions.  Nature \n 519 : 237–41 [ https://www.ncbi.nlm.nih.gov/pubmed/25517090?dopt=AbstractPlus ]\n\nThis set contains class C ’orphan’ G protein coupled receptors where the endogenous ligand(s) is not known.\n Nomenclature  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=209 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=210 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=211 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=258 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=259 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=260 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=261 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=55 \n HGNC, UniProt  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20844 ,  http://www.uniprot.org/uniprot/Q8NFN8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23689 ,  http://www.uniprot.org/uniprot/Q5T848 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:31371 ,  http://www.uniprot.org/uniprot/Q6PRD1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9836 ,  http://www.uniprot.org/uniprot/Q8NFJ5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13308 ,  http://www.uniprot.org/uniprot/Q9NZH0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13309 ,  http://www.uniprot.org/uniprot/Q9NQ84 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13310 ,  http://www.uniprot.org/uniprot/Q9NZD1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18510 ,  http://www.uniprot.org/uniprot/Q5T6X5 \n Comments – – – – – – GPRC6 is a G q ‐coupled receptor which responds to basic amino acids [ http://www.ncbi.nlm.nih.gov/pubmed/15576628?dopt=AbstractPlus ].\nHarpse K  et al . (2017) Structural insight to mutation effects uncover a common allosteric site in class C GPCRs.  Bioinformatics \n 33 : 1116–1120 [ https://www.ncbi.nlm.nih.gov/pubmed/28011766?dopt=AbstractPlus ]\n\nWhilst the taste of acid and salty foods appear to be sensed by regulation of ion channel activity, bitter, sweet and umami tastes are sensed by specialised GPCR. Two classes of taste GPCR have been identified, T1R and T2R, which are similar in sequence and structure to Class C and Class A GPCR, respectively. Activation of taste receptors appears to involve gustducin‐ (Gαt3) and Gα14‐mediated signalling, although the precise mechanisms remain obscure. Gene disruption studies suggest the involvement of PLCβ2 [ http://www.ncbi.nlm.nih.gov/pubmed/12581520?dopt=AbstractPlus ], TRPM5 [ http://www.ncbi.nlm.nih.gov/pubmed/12581520?dopt=AbstractPlus ] and IP3 [ http://www.ncbi.nlm.nih.gov/pubmed/17925404?dopt=AbstractPlus ] receptors in postreceptor signalling of taste receptors. Although predominantly associated with the oral cavity, taste receptors are also located elsewhere, including further down the gastrointestinal system, in the lungs and in the brain.\nT1R3 acts as an obligate partner in T1R1/T1R3 and T1R2/T1R3 heterodimers, which sense umami or sweet, respectively. T1R1/T1R3 heterodimers respond to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  and may be positively allosterically modulated by 5’‐nucleoside monophosphates, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5123  [ http://www.ncbi.nlm.nih.gov/pubmed/12013525?dopt=AbstractPlus ]. T1R2/T1R3 heterodimers respond to sugars, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5411 , and artificial sweeteners, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5432  [ http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=656 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=657 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=658 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14448 ,  http://www.uniprot.org/uniprot/Q7RTX1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14905 ,  http://www.uniprot.org/uniprot/Q8TE23 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15661 ,  http://www.uniprot.org/uniprot/Q7RTX0\nPositive allosteric modulators of T1R2/T1R3 have been reported [2363]. Such compounds enhance the sweet taste of sucrose mediated by these receptors, but are tasteless on their own.\nPalmer RK. (2019) A Pharmacological Perspective on the Study of Taste.  Pharmacol. Rev. \n 71 : 20–48 [ https://www.ncbi.nlm.nih.gov/pubmed/30559245?dopt=AbstractPlus ]\n\nG protein‐coupled receptors → Orphan and other 7TM receptors → Taste 2 receptors\n\nThe composition and stoichiometry of bitter taste receptors is not yet established. Bitter receptors appear to separate into two groups, with very restricted ligand specificity or much broader responsiveness. For example, T2R5 responded to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5433 , but not 10 other bitter compounds [ http://www.ncbi.nlm.nih.gov/pubmed/10761935?dopt=AbstractPlus ], while T2R14 responded to at least eight different bitter tastants, including (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5344 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5344  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2291  [ http://www.ncbi.nlm.nih.gov/pubmed/15178431?dopt=AbstractPlus ].\nSpecialist database  http://bitterdb.agri.huji.ac.il/dbbitter.php  contains additional information on bitter compounds and receptors [ http://www.ncbi.nlm.nih.gov/pubmed/21940398?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=659 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=660 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=661 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=662 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=663 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=664 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=665 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14909 ,  http://www.uniprot.org/uniprot/Q9NYW7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14910 ,  http://www.uniprot.org/uniprot/Q9NYW6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14911 ,  http://www.uniprot.org/uniprot/Q9NYW5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14912 ,  http://www.uniprot.org/uniprot/Q9NYW4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14913 ,  http://www.uniprot.org/uniprot/Q9NYW3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14915 ,  http://www.uniprot.org/uniprot/Q9NYW2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14917 ,  http://www.uniprot.org/uniprot/Q9NYW1 \n \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=666 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=667 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=668 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=669 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=670 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=671 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=673 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14918 ,  http://www.uniprot.org/uniprot/Q9NYW0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14919 ,  http://www.uniprot.org/uniprot/Q9NYV9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14920 ,  http://www.uniprot.org/uniprot/Q9NYV8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14921 ,  http://www.uniprot.org/uniprot/Q9NYV7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19108 ,  http://www.uniprot.org/uniprot/P59542 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19109 ,  http://www.uniprot.org/uniprot/P59543 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19112 ,  http://www.uniprot.org/uniprot/P59541 \n \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=674 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=682 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=675 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=676 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19113 ,  http://www.uniprot.org/uniprot/P59538 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9584 ,  http://www.uniprot.org/uniprot/P59533 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18886 ,  http://www.uniprot.org/uniprot/P59534 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18885 ,  http://www.uniprot.org/uniprot/P59535 \n Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9111  (pIC 50  5.6) [ http://www.ncbi.nlm.nih.gov/pubmed/21650152?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9112  (pIC 50  5.1–5.2) [ http://www.ncbi.nlm.nih.gov/pubmed/20537538?dopt=AbstractPlus ] – – – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=680 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=672 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=678 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2828 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=679 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=677 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=681 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18883 ,  http://www.uniprot.org/uniprot/P59536 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18888 ,  http://www.uniprot.org/uniprot/Q7RTR8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18875 ,  http://www.uniprot.org/uniprot/P59537 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18876 ,  http://www.uniprot.org/uniprot/P59539 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18877 ,  http://www.uniprot.org/uniprot/P59540 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18882 ,  http://www.uniprot.org/uniprot/P59544 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20639 ,  http://www.uniprot.org/uniprot/P59551\nPalmer RK. (2019) A Pharmacological Perspective on the Study of Taste.  Pharmacol. Rev. \n 71 : 20–48 [ https://www.ncbi.nlm.nih.gov/pubmed/30559245?dopt=AbstractPlus ]\n\nNomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=651 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=652 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=655 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=203 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=205 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17830 ,  http://www.uniprot.org/uniprot/Q5VW38 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24300 ,  http://www.uniprot.org/uniprot/Q96N19 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30413 ,  http://www.uniprot.org/uniprot/Q86W33 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20145 ,  http://www.uniprot.org/uniprot/P51810 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23687 ,  http://www.uniprot.org/uniprot/Q5UAW9 \n Endogenous agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3639  [ http://www.ncbi.nlm.nih.gov/pubmed/18828673?dopt=AbstractPlus ] – Comments GPR107 is a member of the LUSTR family of proteins found in both plants and animals, having similar topology to G protein‐coupled receptors [ http://www.ncbi.nlm.nih.gov/pubmed/17454009?dopt=AbstractPlus ] – TPRA1 shows no homology to known G protein‐coupled receptors. Loss‐of‐function mutations underlie ocular albinism type 1 [ http://www.ncbi.nlm.nih.gov/pubmed/7647783?dopt=AbstractPlus ]. GPR157 has ambiguous sequence similarities to several different GPCR families (class A, class B and the slime mould cyclic AMP receptor). Because of its distant relationship to other GPCRs, it cannot be readily classified.\nDavenport AP  et al . (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein‐coupled receptor list: recommendations for new pairings with cognate ligands.  Pharmacol. Rev. \n 65 : 967–86 [ https://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]\nGilissen J  et al . (2016) Insight into SUCNR1 (GPR91) structure and function.  Pharmacol. Ther. \n 159 : 56–65 [ https://www.ncbi.nlm.nih.gov/pubmed/26808164?dopt=AbstractPlus ]\nInsel PA  et al . (2015) G Protein‐Coupled Receptor (GPCR) Expression in Native Cells: “Novel” endoGPCRs as Physiologic Regulators and Therapeutic Targets.  Mol. Pharmacol. \n 88 : 181‐7 [ https://www.ncbi.nlm.nih.gov/pubmed/25737495?dopt=AbstractPlus ]\nKhan MZ  et al . (2017) Neuro‐psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein‐coupled receptors.  Psychopharmacology (Berl.) \n 234 : 1181‐1207 [ https://www.ncbi.nlm.nih.gov/pubmed/28289782?dopt=AbstractPlus ]\nMackenzie AE  et al . (2017) The emerging pharmacology and function of GPR35 in the nervous system.  Neuropharmacology \n 113 : 661–671 [ https://www.ncbi.nlm.nih.gov/pubmed/26232640?dopt=AbstractPlus ]\nNgo T  et al . (2016) Identifying ligands at orphan GPCRs: current status using structure‐based approaches.  Br. J. Pharmacol. \n 173 : 2934‐51 [ https://www.ncbi.nlm.nih.gov/pubmed/26837045?dopt=AbstractPlus ]\n\n5‐HT receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on 5‐HT receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/7938165?dopt=AbstractPlus ]  and subsequently revised  [ http://www.ncbi.nlm.nih.gov/pubmed/8936345?dopt=AbstractPlus ]) are, with the exception of the ionotropic 5‐HT 3  class, GPCRs where the endogenous agonist is  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5 . The diversity of metabotropic 5‐HT receptors is increased by alternative splicing that produces isoforms of the 5‐HT 2A  (non‐functional), 5‐HT 2C  (non‐functional), 5‐HT 4 , 5‐HT 6  (non‐functional) and 5‐HT 7  receptors. Unique amongst the GPCRs, RNA editing produces 5‐HT 2C  receptor isoforms that differ in function, such as efficiency and specificity of coupling to G q/11  and also pharmacology [ http://www.ncbi.nlm.nih.gov/pubmed/16896947?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18554725?dopt=AbstractPlus ]. Most 5‐HT receptors (except 5‐ht 1e  and 5‐ht 5b ) play specific roles mediating functional responses in different tissues (reviewed by [ http://www.ncbi.nlm.nih.gov/pubmed/19086344?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17703282?dopt=AbstractPlus ]).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5286 ,  http://www.uniprot.org/uniprot/P08908 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5287 ,  http://www.uniprot.org/uniprot/P28222 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=30  [ http://www.ncbi.nlm.nih.gov/pubmed/7965808?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7427  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/19499624?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7351  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21486038?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=15  [ http://www.ncbi.nlm.nih.gov/pubmed/10513577?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=45  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=40 [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7191  [ http://www.ncbi.nlm.nih.gov/pubmed/9986723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=60  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7351  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21486038?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=51  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7  [ http://www.ncbi.nlm.nih.gov/pubmed/9495870?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12527336?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15628665?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9067310?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10611634?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760039?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9550290?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1386736?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3924  [ http://www.ncbi.nlm.nih.gov/pubmed/19154445?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3221  [ 1122 ] Antagonists ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=61  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9760039?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=80  (p K \n i  7.9–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9760039?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9550290?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=72  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9336327?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=130  (Inverse agonist) (p K \n i  8.2–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9548813?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11040052?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9776361?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3231  (Inverse agonist) (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10443589?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=113  (p K \n B  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/11888546?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=82  (Antagonist) (p K \n d  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9851589?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3251  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9048968?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=31  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11101361?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15628665?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10431754?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9550290?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3925  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/20799027?dopt=AbstractPlus ], [[ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3252  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15689356?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3227  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16330560?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3219  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/19401496?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=131  (Selective Antagonist) (p K \n d  8.6–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10513577?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10452531?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=117  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605573?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3250  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1738002?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8361548?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=118  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=119  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3926  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/20424633?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=4 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=5 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5289 ,  http://www.uniprot.org/uniprot/P28221 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5291 ,  http://www.uniprot.org/uniprot/P28566 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5292 ,  http://www.uniprot.org/uniprot/P30939 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=121  [ http://www.ncbi.nlm.nih.gov/pubmed/1652050?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9605573?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8967979?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=149  [ http://www.ncbi.nlm.nih.gov/pubmed/10715164?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=15  [ http://www.ncbi.nlm.nih.gov/pubmed/9855638?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=45  [ http://www.ncbi.nlm.nih.gov/pubmed/9303569?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7780656?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=60 [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7191  [ http://www.ncbi.nlm.nih.gov/pubmed/9986723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=51 [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3927  [ 250 ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3927  [ 250 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=40  [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=54  [ http://www.ncbi.nlm.nih.gov/pubmed/9225282?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8380639?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15900510?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3228  [ http://www.ncbi.nlm.nih.gov/pubmed/9632349?dopt=AbstractPlus ] – Gorilla,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=40  [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3928  [ http://www.ncbi.nlm.nih.gov/pubmed/20855361?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=20  [ http://www.ncbi.nlm.nih.gov/pubmed/15900510?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8422  [ http://www.ncbi.nlm.nih.gov/pubmed/21422162?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=21  [ http://www.ncbi.nlm.nih.gov/pubmed/9395253?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=77  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15887956?dopt=AbstractPlus ] – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=118  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=117  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605573?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3250  (Selective Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1738002?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8361548?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=131  (Selective Antagonist) (p K \n d  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10452531?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=119  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10193663?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3248  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1608964?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8863519?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=151  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15900510?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=261  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1328180?dopt=AbstractPlus ] – Mouse \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=6 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=7 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=8 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5293 ,  http://www.uniprot.org/uniprot/P28223 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5294 ,  http://www.uniprot.org/uniprot/P41595 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5295 ,  http://www.uniprot.org/uniprot/P28335 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=147  [ http://www.ncbi.nlm.nih.gov/pubmed/2233697?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933142?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8534270?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=134  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11104741?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459568?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=147  [ http://www.ncbi.nlm.nih.gov/pubmed/8078486?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933142?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12970106?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=147  [ http://www.ncbi.nlm.nih.gov/pubmed/10611640?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933142?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12970106?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=166  [ http://www.ncbi.nlm.nih.gov/pubmed/14709324?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ] Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=161  [ http://www.ncbi.nlm.nih.gov/pubmed/15466450?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12970106?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=166 [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=229  [ http://www.ncbi.nlm.nih.gov/pubmed/15705738?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2941  [ http://www.ncbi.nlm.nih.gov/pubmed/18252809?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=96  (Inverse agonist) (p K \n i  9.3–10) [ http://www.ncbi.nlm.nih.gov/pubmed/12176106?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629531?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8935801?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=135  (p K \n i  7.7–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15107597?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10611634?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=59  (p K \n i  8.8–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/12176106?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8935801?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18308814?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=185  (pIC 50  6.5–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11562430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10188965?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7670  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15686911?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=38  (Inverse agonist) (p K \n i  7.6–9) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9732398?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8935801?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15102927?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9880  (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/29615471?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=135  (p K \n i  7.9–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/10455251?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459568?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=135  (Inverse agonist) (p K \n i  8.3–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10217294?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10611634?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=134  (p K \n i  8.6–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10611640?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=59  (Inverse agonist) (p K \n i  7.9–9) [ http://www.ncbi.nlm.nih.gov/pubmed/10991983?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629531?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18308814?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=47  (Inverse agonist) (p K \n i  8.1–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10991983?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18308814?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=205  (Inverse agonist) (p K \n i  7.8–8) [ http://www.ncbi.nlm.nih.gov/pubmed/10991983?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10991983?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9825  (p K \n i  10.6) [ http://www.ncbi.nlm.nih.gov/pubmed/28943244?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=88  (p K \n i  8.1–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/8845011?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12738034?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8423  (Inverse agonist) (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/17519387?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15102927?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8424  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/25666387?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=188  (p K \n i  9–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/10455251?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=176  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/15107597?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3223  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/17074317?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=193  (p K \n i  8.2–9) [ http://www.ncbi.nlm.nih.gov/pubmed/9225286?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=187  (p K \n i  8.3–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9225287?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3229  (Antagonist) (p K \n d  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/8472747?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=197  (Antagonist) (p K \n d  8.6–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12738034?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3249  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11044889?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3242  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9027929?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=219  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12738034?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3248  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8450835?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=232  (Antagonist, Inverse agonist) (p K \n d  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15322733?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=169  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=232  (Antagonist, Inverse agonist) (p K \n d  8.7–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10217294?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12738034?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=169  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10217294?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=219  (Agonist) \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=9 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=10 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=648 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5299 ,  http://www.uniprot.org/uniprot/Q13639 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5300 ,  http://www.uniprot.org/uniprot/P47898 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16291 , – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=240  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11218067?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10646498?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7796807?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10683202?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9349523?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8426  [ http://www.ncbi.nlm.nih.gov/pubmed/23756062?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=235  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12801225?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9603189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10683202?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10821780?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3230  [ http://www.ncbi.nlm.nih.gov/pubmed/8903510?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8427  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/25316608?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8425  [ http://www.ncbi.nlm.nih.gov/pubmed/22959244?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18415081?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=234  [ http://www.ncbi.nlm.nih.gov/pubmed/9351641?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=250  (p K \n i  8.7–12.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9351641?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15351779?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=256  (p K \n i  9.8–10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10646498?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10683202?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9349523?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=247  (p K i 9.3–10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11218067?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10646498?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9603189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15351779?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9349523?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=264  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/16002289?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=259  (Antagonist) (p K \n d  9.7–10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11218067?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10646498?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10821780?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9349523?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3243  (Antagonist) (p K \n d  10.1) [ 251 ] – Pig, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=239  (Selective Antagonist) (p K \n d  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9225293?dopt=AbstractPlus ] – Guinea pig, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3244  (Antagonist) (p K \n d  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/21831646?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=261  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11343685?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=262  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11343685?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=261  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8450829?dopt=AbstractPlus ] – Mouse, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=262  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9928243?dopt=AbstractPlus ] – Mouse \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=11 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=12 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5301 ,  http://www.uniprot.org/uniprot/P50406 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5302 ,  http://www.uniprot.org/uniprot/P34969 \n Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3240  [ http://www.ncbi.nlm.nih.gov/pubmed/17625499?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3217  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15771424?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8429  [ http://www.ncbi.nlm.nih.gov/pubmed/19523834?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8428  [ http://www.ncbi.nlm.nih.gov/pubmed/16055331?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8434  [ http://www.ncbi.nlm.nih.gov/pubmed/17649988?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8435 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8436  [ http://www.ncbi.nlm.nih.gov/pubmed/18800769?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8433  [ http://www.ncbi.nlm.nih.gov/pubmed/23541835?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3929  [ http://www.ncbi.nlm.nih.gov/pubmed/19118950?dopt=AbstractPlus ] Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7461  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/20404009?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=90  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7908055?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7351  (p K \n i  6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21486038?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3241  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/17069795?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=276  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9925723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7356  (p K \n i  8.9) [ 407 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3235  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11140733?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=275  (p K \n i  7.9–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9730917?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9647481?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3233  (p K \n i  8.6–8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10807680?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3237  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12392747?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8431  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12825922?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10052959?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8432  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/22570363?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=281  (Inverse agonist) (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9720804?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8430  (Antagonist) (p K \n i  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/22223878?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3245  (Selective Antagonist) (p K \n d  9) [ http://www.ncbi.nlm.nih.gov/pubmed/17069795?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=219  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9284367?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3246  (Antagonist) (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9730917?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=262  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=262  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10807680?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3248  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8226867?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9303561?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3247  (Selective Antagonist) (p K \n d  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10807680?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=219  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9303561?dopt=AbstractPlus ]\nTabulated  pK \n i  and  K \n D  values refer to binding to human 5‐HT receptors unless indicated otherwise. The nomenclature of 5‐HT 1B /5‐HT 1D  receptors has been revised [ http://www.ncbi.nlm.nih.gov/pubmed/8936345?dopt=AbstractPlus ]. Only the non‐rodent form of the receptor was previously called 5‐HT 1D : the human 5‐HT 1B  receptor (tabulated) displays a different pharmacology to the rodent forms of the receptor due to Thr335 of the human sequence being replaced by Asn in rodent receptors [ http://www.ncbi.nlm.nih.gov/pubmed/18571247?dopt=AbstractPlus ]. Wang  et al.  (2013) report X‐ray structures which reveal the binding modality of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=149  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=121  (DHE) to the 5‐HT 1B  receptor in comparison with the structure of the 5HT 2B  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/23519210?dopt=AbstractPlus ]; some of these drugs adopt rather different conformations depending on the target receptor [ http://www.ncbi.nlm.nih.gov/pubmed/29398112?dopt=AbstractPlus ]. Various 5‐HT receptors have multiple partners in addition to G proteins, which may affect function and pharmacology [ http://www.ncbi.nlm.nih.gov/pubmed/21777185?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3226  is a selective antagonist of the rodent 5‐HT 1B  receptor.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5434  (LSD) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=88  bind with high affinity to dopamine D4 and histamine H 1  receptors respectively, and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=88  is a potent α1 adrenoceptor antagonist, in addition to blocking 5‐HT 2A  receptors.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=139  (LSD) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=149  show a strong preference for arrestin recruitment over G protein coupling at the 5‐HT 2B  receptor, with no such preference evident at 5‐HT 1B  receptors, and they also antagonise 5‐HT 7A  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/23519215?dopt=AbstractPlus ]. DHE ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=282 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=48  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=37  also show significant preference for arrestin recruitment over G protein coupling at 5‐HT 2B  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/23519215?dopt=AbstractPlus ]. The 5‐HT 2B  (and other 5‐HT) receptors interact with immunocompetent cells [ http://www.ncbi.nlm.nih.gov/pubmed/28265714?dopt=AbstractPlus ]. The serotonin antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=206  was key to the discovery of the 5HT 2C  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/6519175?dopt=AbstractPlus ], initially known as 5‐HT 1C  [ http://www.ncbi.nlm.nih.gov/pubmed/28806488?dopt=AbstractPlus ]. The human 5‐HT 5A  receptor may couple to several signal transduction pathways when stably expressed in C6 glioma cells [ http://www.ncbi.nlm.nih.gov/pubmed/12558985?dopt=AbstractPlus ] and rodent prefrontal cortex (layer V pyramidal neurons) [ http://www.ncbi.nlm.nih.gov/pubmed/22539842?dopt=AbstractPlus ]. The human orthologue of the mouse 5‐ht 5b  receptor is non‐functional (stop codons); the 5‐ht 1e  receptor has not been cloned from mouse, or rat, impeding definition of its function [ http://www.ncbi.nlm.nih.gov/pubmed/18571247?dopt=AbstractPlus ]. In addition to accepted receptors, an ’orphan’ receptor, unofficially termed5‐HT 1P , has been described [ http://www.ncbi.nlm.nih.gov/pubmed/10429737?dopt=AbstractPlus ].\nBockaert J  et al . (2011) 5‐HT(4) receptors, a place in the sun: act two.  Curr Opin Pharmacol \n 11 : 87‐93 [ https://www.ncbi.nlm.nih.gov/pubmed/21342787?dopt=AbstractPlus ]\nHayes DJ  et al . (2011) 5‐HT receptors and reward‐related behaviour: a review.  Neurosci Biobehav Rev \n 35 : 1419‐49 [ https://www.ncbi.nlm.nih.gov/pubmed/21402098?dopt=AbstractPlus ]\nHoyer D  et al . (1994) International Union of Pharmacology classification of receptors for 5hydroxytryptamine (Serotonin).  Pharmacol. Rev. \n 46 : 157‐203 [ https://www.ncbi.nlm.nih.gov/pubmed/7938165?dopt=AbstractPlus ]\nLeopoldo M  et al . (2011)Serotonin 5‐HT 7  receptor agents: Structure‐activity relationships and potential therapeutic applications in central nervous system disorders.  Pharmacol. Ther. \n 129 : 120‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/20923682?dopt=AbstractPlus ]\nMeltzer HY  et al . (2011) The role of serotonin receptors in the action of atypical antipsychotic drugs.  Curr Opin Pharmacol \n 11 : 59‐67 [ https://www.ncbi.nlm.nih.gov/pubmed/21420906?dopt=AbstractPlus ]\nRoberts AJ  et al . (2012) The 5‐HT(7) receptor in learning and memory.  Hippocampus \n 22 : 762‐71 [ https://www.ncbi.nlm.nih.gov/pubmed/21484935?dopt=AbstractPlus ]\n\nMuscarinic acetylcholine receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Muscarinic Acetylcholine Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/9647869?dopt=AbstractPlus ]) are GPCRs of the Class A, rhodopsin‐like family where the endogenous agonist is  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=294 . In addition to the agents listed in the table,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=289 , its structural analogues  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=334  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3271 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=333 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3258  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5435  have been described as functionally selective agonists of the M 1  receptor subtype  via  binding in a mode distinct from that utilized by non‐selective agonists [ http://www.ncbi.nlm.nih.gov/pubmed/20413650?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18842902?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18454168?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16207821?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17525129?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20684563?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16959945?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12021390?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14595031?dopt=AbstractPlus ]. There are two pharmacologically characterised allosteric sites on muscarinic receptors, one defined by it binding  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=356 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=347  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=342 , and the other defined by the binding of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=337 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=340 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=339  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=346  [ http://www.ncbi.nlm.nih.gov/pubmed/10860942?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12435818?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=13 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=14 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1950 ,  http://www.uniprot.org/uniprot/P11229 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1951 ,  http://www.uniprot.org/uniprot/P08172 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=298  [ http://www.ncbi.nlm.nih.gov/pubmed/9614217?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10323594?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=305  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=297 [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=298  [ http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9454790?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=297 [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10259  [ http://www.ncbi.nlm.nih.gov/pubmed/30276808?dopt=AbstractPlus ] – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7459  (pIC 50  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/21036043?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8586  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=320  (p K \n i  8.5–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9614217?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16439611?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12049493?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9029489?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=367  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/8441333?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=307  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/1994002?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=367  (p K \n i  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/8441333?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7459  (pIC 50  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21036043?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=320  (p K \n i  7.8–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/2704370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12049493?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9454790?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16188951?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8586  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=360  (Inverse agonist) (p K \n i  8.4–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9671109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7128  (p K \n d  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/1346637?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3274  (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19407080?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3276  (p K \n i  7.3–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10323493?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8813552?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=361  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/7805774?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=314  (Negative) (p K \n i  11–11.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10799315?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8549  (Positive) (p K B 6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/25326383?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=337  (Positive) (p K \n d  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10860942?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=342  (Positive) (p K \n d  4.5–5.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9495826?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5436  (Positive) (p K \n B  4–4.8) [ http://www.ncbi.nlm.nih.gov/pubmed/25326383?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24443568?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22086918?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19717450?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3261  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/19047481?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3259  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/19047481?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=362  (Negative) (p K \n d  6–7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/15163212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12815174?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7634  (Negative) (p K \n d  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9890565?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=341  (Negative) (p K \n d  6.1–6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=356  (Negative) (p K \n d  5.9–6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/990587?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651370?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6938  (Positive) (p K \n d  5.7) [ http://www.ncbi.nlm.nih.gov/pubmed/24807965?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24256733?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3262  (Positive) (p K \n d  4.4) [ http://www.ncbi.nlm.nih.gov/pubmed/21989256?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=318  (Antagonist) (p K \n d  10.6–10.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11578621?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8598  (Antagonist) (p K \n d  10.5) [ http://www.ncbi.nlm.nih.gov/pubmed/20133736?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=317  (Antagonist) (p K \n d  9.4–10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9846649?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9614217?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16675658?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16369696?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651370?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8594  (Antagonist) (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/2704371?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8600  (Antagonist) (p K \n d  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/20133736?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3272  (Antagonist) (p K \n d  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/6546354?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=318  (Antagonist) (p K \n d  10.1–10.6) [ http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8598  (Antagonist) (p K \n i  10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/23357106?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8592  (Antagonist) (p K \n d  10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/23435542?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=317  (Antagonist) (p K \n d  9.3–9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9846649?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16675658?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16369696?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7687290?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8600  (Antagonist) (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/23357106?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8593  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/14722259?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8595  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/6478115?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=364  (Allosteric modulator, Positive) (p K \n d  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/12815174?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3266  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12668051?dopt=AbstractPlus ] – Mouse \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=15 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=16 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=17 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1952 ,  http://www.uniprot.org/uniprot/P20309 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1953 ,  http://www.uniprot.org/uniprot/P08173 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1954 ,  http://www.uniprot.org/uniprot/P08912 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=305  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=298  [ http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10323594?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=297 ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=305  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=298 [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10323594?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=297 [ http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=305  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16002459?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=298  [ http://www.ncbi.nlm.nih.gov/pubmed/10323594?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=367  (p K \n i  9.5–11.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8441333?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16847442?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8586  (p K i 9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=320  (p K \n i  8.9–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/2704370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12049493?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9029489?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=325  (p K \n i  9.3–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/16847442?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7449  (pIC 50  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19653626?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7459  (pIC 50  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/21036043?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8586  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=307  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/1994002?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=359  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7128  (p K \n d  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/1346637?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8583  (p K i 8.3–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9671109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2043926?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7459  (pIC 50  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/21036043?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8586  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/20590605?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=307  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/1994002?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=360  (p K \n i  8.5–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9671109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9671109?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=321  (p K \n i  7.9–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9671109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9113359?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ] Selective antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8591  (p K \n i  6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/24692176?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=340  (Positive) (p K \n d  5.1) [ http://www.ncbi.nlm.nih.gov/pubmed/12435818?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=344  (Positive) (p K \n d  3.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9495826?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=313  (Negative) (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9862767?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3263  (Positive) (pEC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/18772318?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3256  (Positive) (pEC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/18772318?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6938  (Positive) (p K \n d  5.7) [ http://www.ncbi.nlm.nih.gov/pubmed/24807965?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=348  (Positive) (p K \n d  4) [ http://www.ncbi.nlm.nih.gov/pubmed/14722259?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3262  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/18678919?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8687  (Positive) (pEC 50  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/27461343?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25147929?dopt=AbstractPlus ] Selective allosteric modulators – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7631  (Negative) (pIC 50  6.5) [ http://www.ncbi.nlm.nih.gov/pubmed/24164599?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8592  (Antagonist) (p K \n d  10.7) [ http://www.ncbi.nlm.nih.gov/pubmed/23435542?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=318  (Antagonist) (p K \n d  10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=317  (Antagonist) (p K \n d  9.7–10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9846649?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12049493?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16369696?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651370?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=319  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9029489?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=318  (Antagonist) (p K \n d  9.7–10.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11578621?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/3443095?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=317  (Antagonist) (p K \n d  9.9–10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9846649?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9224827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16369696?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9862767?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7687290?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8593  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/14722259?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=318  (Antagonist) (p K \n d  10.2–10.7), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=317  (Antagonist) (p K \n d  9.3–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9846649?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12235229?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11303071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16369696?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7687290?dopt=AbstractPlus ]\nThe crystal structures of the M 1 ‐M4 receptor subtypes have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/22278061?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26958838?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22358838?dopt=AbstractPlus ]. Direct activation  via  an allosteric site has been reported for M 1  receptors ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5436 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9228 ) and M4 receptors ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3262 ) [ http://www.ncbi.nlm.nih.gov/pubmed/27275946?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21300722?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19940843?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19717450?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20406819?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18628403?dopt=AbstractPlus ]. The allosteric site for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=356  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=347  on M 2  receptors can be labelled by [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=364  [ http://www.ncbi.nlm.nih.gov/pubmed/12815174?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=290  is a functionally selective partial agonist that appears to interact in a bitopic mode with both the orthosteric and an allosteric site on the M 2  muscarinic receptor [ http://www.ncbi.nlm.nih.gov/pubmed/18723515?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3255 , hybrid 1 and hybrid 2, are multivalent (bitopic) ligands that also achieve selectivity for M 2  receptors by binding both to the orthosteric and a nearby allosteric site [ http://www.ncbi.nlm.nih.gov/pubmed/18842964?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17478612?dopt=AbstractPlus ].\nAlthough numerous ligands for muscarinic acetylcholine receptors have been described, relatively few selective antagonists have been described, so it is common to assess the rank order of affinity of a number of antagonists of limited selectivity ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=307 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=321 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=328 ) in order to identify the involvement of particular subtypes. It should be noted that the measured affinities of antagonists (and agonists) in radioligand binding studies are sensitive to ionic strength and can increase over 10‐fold at low ionic strength compared to their values at physiological ionic strengths [ http://www.ncbi.nlm.nih.gov/pubmed/497538?dopt=AbstractPlus ].\nBurger WAC  et al . (2018) Toward an understanding of the structural basis of allostery in muscarinic acetylcholine receptors.  J Gen Physiol \n 150 : 1360‐1372 [ https://www.ncbi.nlm.nih.gov/pubmed/30190312?dopt=AbstractPlus ]\nCaulfield MP  et al . (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors.  Pharmacol Rev \n 50 : 279‐290 [ https://www.ncbi.nlm.nih.gov/pubmed/9647869?dopt=AbstractPlus ]\nEglen RM. (2012) Overview of muscarinic receptor subtypes.  Handb Exp Pharmacol  3‐28 [ https://www.ncbi.nlm.nih.gov/pubmed/22222692?dopt=AbstractPlus ]\nKruse AC  et al . (2014) Muscarinic acetylcholine receptors: novel opportunities for drug development.  Nat Rev Drug Discov \n 13 : 549‐60 [ https://www.ncbi.nlm.nih.gov/pubmed/24903776?dopt=AbstractPlus ]\nLeach K  et al . (2012) Structure‐function studies of muscarinic acetylcholine receptors.  Handb Exp Pharmacol  29‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/22222693?dopt=AbstractPlus ]\nValant C  et al . (2012) The best of both worlds? Bitopic orthosteric/allosteric ligands of g proteincoupled receptors.  Annu Rev Pharmacol Toxicol \n 52 : 153‐78 [ https://www.ncbi.nlm.nih.gov/pubmed/21910627?dopt=AbstractPlus ]\n\nAdenosine receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Adenosine Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/11734617?dopt=AbstractPlus ]) are activated by the endogenous ligand  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2844  (potentially  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4554  also at A 3  receptors). Crystal structures for the antagonist‐bound [ http://www.ncbi.nlm.nih.gov/pubmed/22220592?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18832607?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22798613?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27312113?dopt=AbstractPlus ], agonist‐bound [ http://www.ncbi.nlm.nih.gov/pubmed/25762024?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21593763?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21393508?dopt=AbstractPlus ] and G protein‐bound A 2A  adenosine receptors [ http://www.ncbi.nlm.nih.gov/pubmed/27462812?dopt=AbstractPlus ] have been described. The structures of an antagonist‐bound A1 receptor [ http://www.ncbi.nlm.nih.gov/pubmed/28235198?dopt=AbstractPlus ] and an adenosine‐bound A1 receptor‐G i  complex [ http://www.ncbi.nlm.nih.gov/pubmed/29925945?dopt=AbstractPlus ] have been resolved by cryo‐electronmicroscopy. Another structure of an antagonist‐bound A1 receptor obtained with X‐ray crystallography has also been reported [ http://www.ncbi.nlm.nih.gov/pubmed/28712806?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=18 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=19 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=20 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=21 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:262 ,  http://www.uniprot.org/uniprot/P30542 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:263 ,  http://www.uniprot.org/uniprot/P29274 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:264 ,  http://www.uniprot.org/uniprot/P29275 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:268 ,  http://www.uniprot.org/uniprot/P0DMS8 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2844  [ http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2844  [ http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2844  [ http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2844  [ http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=377  [ http://www.ncbi.nlm.nih.gov/pubmed/15476669?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7798201?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920910?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8300561?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=377  [ http://www.ncbi.nlm.nih.gov/pubmed/15267242?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9179373?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15476669?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7775460?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920286?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=377  [ http://www.ncbi.nlm.nih.gov/pubmed/11093773?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15267242?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11266650?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10496952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15194002?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16219300?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=377  [ http://www.ncbi.nlm.nih.gov/pubmed/15267242?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15476669?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9364471?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8234299?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10779381?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14662005?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=380  [ http://www.ncbi.nlm.nih.gov/pubmed/9827575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15740718?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15476669?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16444290?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16518376?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7798201?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920910?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6560 )‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6560  [ http://www.ncbi.nlm.nih.gov/pubmed/19317449?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5590  [ http://www.ncbi.nlm.nih.gov/pubmed/12672250?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=374 [ http://www.ncbi.nlm.nih.gov/pubmed/16518376?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16020631?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10235  [ http://www.ncbi.nlm.nih.gov/pubmed/30605331?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3290  [ http://www.ncbi.nlm.nih.gov/pubmed/11406470?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8420  [ http://www.ncbi.nlm.nih.gov/pubmed/22324512?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21393508?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9236  [ http://www.ncbi.nlm.nih.gov/pubmed/22220592?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=375  [ http://www.ncbi.nlm.nih.gov/pubmed/15267242?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9179373?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15476669?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16518376?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7775460?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920286?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16020631?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5596 [ http://www.ncbi.nlm.nih.gov/pubmed/16518376?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3289  [ http://www.ncbi.nlm.nih.gov/pubmed/17353435?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=422  [ http://www.ncbi.nlm.nih.gov/pubmed/11705449?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8126704?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10779381?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=457  [ http://www.ncbi.nlm.nih.gov/pubmed/10731034?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9364471?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7932588?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8421  [ http://www.ncbi.nlm.nih.gov/pubmed/22559880?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=384  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=404  (p K \n d  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/19317449?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=384  (p K \n i  7.7–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9179373?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7775460?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=404  (p K \n i  8.4–9) [ http://www.ncbi.nlm.nih.gov/pubmed/9179373?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9179373?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=404  (p K \n i  6.9–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11093773?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11266650?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10624567?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10496952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15194002?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=384  (p K \n i  6–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/19141710?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10624567?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15194002?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=384  (p K \n i  7–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/8863790?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10779381?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=404  (p K \n i  7–7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8234299?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3285  (p K \n i  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/14563788?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=386  (p K i 7.4–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/15740718?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8032613?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16020631?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920910?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16902942?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3281  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/17558436?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8419  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/8632314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9530  (p K \n i  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/28235198?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3283  (p K \n i  8.4–10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/20801028?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11087559?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=405  (p K \n i  8.8–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6561  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/19569717?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3284  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/19569717?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=449  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11266650?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10737749?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3286  (p K \n i  7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11906291?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=448  (p K \n i  8.2–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9364471?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8863790?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11226132?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16553647?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3280  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10841801?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=474  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9703464?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=470  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9364471?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8917655?dopt=AbstractPlus ,  1273 ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9445  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/2174510?dopt=AbstractPlus ] – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9446  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/16722654?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9447  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/19161279?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=379  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920910?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=406  (Antagonist) (p K \n d  8.4–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9827575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11705449?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9920910?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8300561?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=455  (Antagonist) (p K \n d  8.7–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/11164377?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10927024?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=424  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2600819?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2213023?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=453  (Antagonist) (p K \n d  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11266650?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=436  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9933143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10779381?dopt=AbstractPlus ]\nAdenosine inhibits many intracellular ATP‐utilising enzymes, including adenylyl cyclase (P‐site). A pseudogene exists for the A 2B  adenosine receptor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:265 ) with 79% identity to the A 2B  adenosine receptor cDNA coding sequence, but which is unable to encode a functional receptor [ http://www.ncbi.nlm.nih.gov/pubmed/7558011?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=386  also exhibits antagonism at A 2B  receptors (p K i ca. 7,[ http://www.ncbi.nlm.nih.gov/pubmed/8937736?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ]). Antagonists at A 3  receptors exhibit marked species differences, such that only  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=474  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=470  are selective at the rat A 3  receptor. In the absence of other adenosine receptors, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=406  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=455  can also be used to label A 2B  receptors (KD  ca . 30 and 60 nM respectively). [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=436  also binds to A 1  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/9459566?dopt=AbstractPlus ]. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=424  is relatively selective for A 2A  receptors, but may also bind to other sites in cerebral cortex [ http://www.ncbi.nlm.nih.gov/pubmed/8692280?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7566470?dopt=AbstractPlus ]. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=425  binds to other non‐receptor elements, which also recognise adenosine [ http://www.ncbi.nlm.nih.gov/pubmed/8937447?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3279  has been described as a fluorescent antagonist for labelling A 1  adenosine receptors in living cells, although activity at other adenosine receptors was not examined [ http://www.ncbi.nlm.nih.gov/pubmed/15070776?dopt=AbstractPlus ].\nBorea PA  et al . (2015) The A 3  adenosine receptor: history and perspectives.  Pharmacol Rev \n 67 : 74‐102 [ https://www.ncbi.nlm.nih.gov/pubmed/25387804?dopt=AbstractPlus ]\nCronstein BN  et al . (2017) Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases.  Nat Rev Rheumatol \n 13 : 41‐51 [ https://www.ncbi.nlm.nih.gov/pubmed/27829671?dopt=AbstractPlus ]\nFredholm BB  et al . (2011) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors–an update.  Pharmacol Rev \n 63 : 1‐34 [ https://www.ncbi.nlm.nih.gov/pubmed/21303899?dopt=AbstractPlus ]\nGuo D  et al . (2017) Kinetic Aspects of the Interaction between Ligand and G Protein‐Coupled Receptor: The Case of the Adenosine Receptors.  Chem Rev \n 117 : 38‐66 [ https://www.ncbi.nlm.nih.gov/pubmed/27088232?dopt=AbstractPlus ]\nGöblyös A  et al . (2011) Allosteric modulation of adenosine receptors.  Biochim Biophys Acta \n 1808 : 1309‐18 [ https://www.ncbi.nlm.nih.gov/pubmed/20599682?dopt=AbstractPlus ]\nLasley RD. (2011) Adenosine receptors and membrane microdomains.  Biochim Biophys Acta \n 1808 : 1284‐9 [ https://www.ncbi.nlm.nih.gov/pubmed/20888790?dopt=AbstractPlus ]\nMundell S  et al . (2011) Adenosine receptor desensitization and trafficking.  Biochim Biophys Acta \n 1808 : 1319‐28 [ https://www.ncbi.nlm.nih.gov/pubmed/20550943?dopt=AbstractPlus ]\nVecchio EA  et al . (2018) New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism.  Br J Pharmacol \n 175 : 4036‐4046 [ https://www.ncbi.nlm.nih.gov/pubmed/29679502?dopt=AbstractPlus ]\nWei CJ  etal . (2011)Normaland abnormalfunctions ofadenosine receptors inthecentral nervous system revealed by genetic knockout studies.  Biochim Biophys Acta \n 1808 : 1358‐79[ https://www.ncbi.nlm.nih.gov/pubmed/21185258?dopt=AbstractPlus ]\n\nAdhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysisinducing (GAIN) domain [ http://www.ncbi.nlm.nih.gov/pubmed/22333914?dopt=AbstractPlus ] containing a GPCR proteolytic site. The N‐terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter‐ and matricellular interactions and leading to the term adhesion GPCR [ http://www.ncbi.nlm.nih.gov/pubmed/12761335?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18789697?dopt=AbstractPlus ]. Several receptors have been suggested to function as mechanosensors [ http://www.ncbi.nlm.nih.gov/pubmed/26841242?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25695270?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25937282?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26499266?dopt=AbstractPlus ].  The nomenclature of these receptors was revised in 2015 as recommended by \n NC‐IUPHAR \n and the \n Adhesion GPCR Consortium  [ http://www.ncbi.nlm.nih.gov/pubmed/25713288?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=197 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=198 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=199 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=174 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=175 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=176 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13838 ,  http://www.uniprot.org/uniprot/Q86SQ6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17849 ,  http://www.uniprot.org/uniprot/Q96PE1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13839 ,  http://www.uniprot.org/uniprot/Q8IWK6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:943 ,  http://www.uniprot.org/uniprot/O14514 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:944 ,  http://www.uniprot.org/uniprot/O60241 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:945 ,  http://www.uniprot.org/uniprot/O60242 \n Endogenous agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3638  [ http://www.ncbi.nlm.nih.gov/pubmed/17960134?dopt=AbstractPlus ] – – Comments – Required to assemble higher‐order Reck/Gpr124/Frizzled/ Lrp5/6 complexes [ http://www.ncbi.nlm.nih.gov/pubmed/30026314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25558062?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30304675?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26051822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25373781?dopt=AbstractPlus ]. – Reported to mediate phagocytosis through binding of phosphatidylserine [ http://www.ncbi.nlm.nih.gov/pubmed/17960134?dopt=AbstractPlus ] and lipopolysaccharide [ http://www.ncbi.nlm.nih.gov/pubmed/21245295?dopt=AbstractPlus ]. – Reported to bind C1q‐like molecules [ http://www.ncbi.nlm.nih.gov/pubmed/21262840?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=178 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=179 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=180 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=202 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=204 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1850 ,  http://www.uniprot.org/uniprot/Q9NYQ6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3231 ,  http://www.uniprot.org/uniprot/Q9HCU4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3230 ,  http://www.uniprot.org/uniprot/Q9NYQ7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19893 ,  http://www.uniprot.org/uniprot/Q6QNK2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18651 ,  http://www.uniprot.org/uniprot/Q7Z7M1 \n Comments – Mutated in Joubert syndrome patients [ http://www.ncbi.nlm.nih.gov/pubmed/28052552?dopt=AbstractPlus ]. High‐confidence risk gene for Tourette syndrome [ http://www.ncbi.nlm.nih.gov/pubmed/30257206?dopt=AbstractPlus ]. Is a G s  protein‐coupled receptor [ http://www.ncbi.nlm.nih.gov/pubmed/22025619?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25533341?dopt=AbstractPlus ] and highly expressed in glioblastoma [ http://www.ncbi.nlm.nih.gov/pubmed/27775701?dopt=AbstractPlus ]. – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=182 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=183 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=184 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=185 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=177 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3336 ,  http://www.uniprot.org/uniprot/Q14246 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3337 ,  http://www.uniprot.org/uniprot/Q9UHX3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23647 ,  http://www.uniprot.org/uniprot/Q9BY15 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19240 ,  http://www.uniprot.org/uniprot/Q86SQ3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1711 ,  http://www.uniprot.org/uniprot/P48960 \n Comments – A mutation destabilizing the GAIN domain sensitizes mast cells to IgE‐independent vibration‐induced degranulation [ http://www.ncbi.nlm.nih.gov/pubmed/26841242?dopt=AbstractPlus ]. Reported to bind chondroitin sulfate B [ http://www.ncbi.nlm.nih.gov/pubmed/12829604?dopt=AbstractPlus ]. – – Reported to bind CD55 [ http://www.ncbi.nlm.nih.gov/pubmed/9064337?dopt=AbstractPlus ], chondroitin sulfate B [ http://www.ncbi.nlm.nih.gov/pubmed/12829604?dopt=AbstractPlus ], α 5 β 1  and αγβ 3  integrins [ http://www.ncbi.nlm.nih.gov/pubmed/15576472?dopt=AbstractPlus ], and CD90 [ http://www.ncbi.nlm.nih.gov/pubmed/22210915?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=190 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=191 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=193 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=195 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=196 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18990 ,  http://www.uniprot.org/uniprot/Q5T601 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18991 ,  http://www.uniprot.org/uniprot/Q8IZF7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18989 ,  http://www.uniprot.org/uniprot/Q8IZF5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19011 ,  http://www.uniprot.org/uniprot/Q8IZF3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19030 ,  http://www.uniprot.org/uniprot/Q8IZF2 \n Comments Synaptamide is an agonist at ADGRF1 supporting neurogenesis [ http://www.ncbi.nlm.nih.gov/pubmed/27759003?dopt=AbstractPlus ] and couples to Gs and Gq pathways [ http://www.ncbi.nlm.nih.gov/pubmed/28154189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25918380?dopt=AbstractPlus ]. ADGRF2 is highly expressed in squamous epithelia and gene deficiency did not result in detectable defects [ http://www.ncbi.nlm.nih.gov/pubmed/22837050?dopt=AbstractPlus ]. ADGRF3 is highly expressed in gastrointestinal neuroendocrine tumors [ http://www.ncbi.nlm.nih.gov/pubmed/23158174?dopt=AbstractPlus ]. ADGRF4 couples to G q/11  proteins [ http://www.ncbi.nlm.nih.gov/pubmed/28154189?dopt=AbstractPlus ], is highly expressed in squamous epithelia and gene deficiency did not result in detectable defects [ http://www.ncbi.nlm.nih.gov/pubmed/22837050?dopt=AbstractPlus ]. ADGRF5 controls alveolar surfactant secretion via G q/11  pathway [ http://www.ncbi.nlm.nih.gov/pubmed/28570277?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=186 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=187 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=188 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=192 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=194 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=200 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=201 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4512 ,  http://www.uniprot.org/uniprot/Q9Y653 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4516 ,  http://www.uniprot.org/uniprot/Q8IZP9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13728 ,  http://www.uniprot.org/uniprot/Q86Y34 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18992 ,  http://www.uniprot.org/uniprot/Q8IZF6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19010 ,  http://www.uniprot.org/uniprot/Q8IZF4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13841 ,  http://www.uniprot.org/uniprot/Q86SQ4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19241 ,  http://www.uniprot.org/uniprot/Q96K78 \n Comments Reported to bind tissue transglutaminase 2 [ http://www.ncbi.nlm.nih.gov/pubmed/16757564?dopt=AbstractPlus ] and collagen, which activates the G 12/13  pathway [ http://www.ncbi.nlm.nih.gov/pubmed/21768377?dopt=AbstractPlus ]. ADGRG2 is coupled to G q  and G s  pathways [ http://www.ncbi.nlm.nih.gov/pubmed/26188515?dopt=AbstractPlus ] and gene deficiency causes congenital obstructive azoospermia [ http://www.ncbi.nlm.nih.gov/pubmed/27476656?dopt=AbstractPlus ]. ADGRG3 is expressed in immune cells [ http://www.ncbi.nlm.nih.gov/pubmed/27089991?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24113187?dopt=AbstractPlus ] and couples to G o  proteins [ http://www.ncbi.nlm.nih.gov/pubmed/22575658?dopt=AbstractPlus ]. ADGRG4 is highly expressed in enterochromaffin cells and gastrointestinal neuroendocrine tumors [ http://www.ncbi.nlm.nih.gov/pubmed/18953328?dopt=AbstractPlus ]. ADGRG5 is a constitutively active G s  protein‐coupled receptor [ http://www.ncbi.nlm.nih.gov/pubmed/22575658?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26499266?dopt=AbstractPlus ], highly expressed in eosinophils and NK cells [ http://www.ncbi.nlm.nih.gov/pubmed/21724806?dopt=AbstractPlus ]. ADGRG6 is a key regulator of Schwann cell‐mediated myelination [ http://www.ncbi.nlm.nih.gov/pubmed/19745155?dopt=AbstractPlus ], and couples to G s  and G i/o  pathways [ http://www.ncbi.nlm.nih.gov/pubmed/24227709?dopt=AbstractPlus ]. ADGRG7 is expressed in interstine and involved in interstine contractility regulation [ http://www.ncbi.nlm.nih.gov/pubmed/24574718?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=206 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=207 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=208 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=181 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=189 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20973 ,  http://www.uniprot.org/uniprot/O94910 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18582 ,  http://www.uniprot.org/uniprot/O95490 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20974 ,  http://www.uniprot.org/uniprot/Q9HAR2 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20822 ,  http://www.uniprot.org/uniprot/Q9HBW9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17416 ,  http://www.uniprot.org/uniprot/Q8WXG9 \n Comments Couples to G s  and G q  pathways [ http://www.ncbi.nlm.nih.gov/pubmed/9261169?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26505631?dopt=AbstractPlus ]. – A LPHN3 gene variant in humans is associated with attention‐deficit‐hyperactivity disorder [ http://www.ncbi.nlm.nih.gov/pubmed/20157310?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28472652?dopt=AbstractPlus ]. – Loss‐of‐function mutations are associated with Usher syndrome, a sensory deficit disorder [ http://www.ncbi.nlm.nih.gov/pubmed/18463160?dopt=AbstractPlus ].\nHamann J et al. (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein‐coupled receptors.  Pharmacol Rev \n 67 : 338‐67 [ https://www.ncbi.nlm.nih.gov/pubmed/25713288?dopt=AbstractPlus ]\nLangenhan T et al. (2013) Sticky signaling–adhesion class G protein‐coupled receptors take the stage.  Sci Signal \n 6 : re3 [ https://www.ncbi.nlm.nih.gov/pubmed/23695165?dopt=AbstractPlus ]\nLiebscher I et al. (2016) Tethered Agonism: A Common Activation Mechanism of Adhesion GPCRs.  Handb Exp Pharmacol \n 234 : 111‐125 [ https://www.ncbi.nlm.nih.gov/pubmed/27832486?dopt=AbstractPlus ]\nMonk KR et al. (2015) Adhesion G Protein‐Coupled Receptors: From In Vitro Pharmacology to In Vivo Mechanisms.  Mol Pharmacol \n 88 : 617‐23 [ https://www.ncbi.nlm.nih.gov/pubmed/25956432?dopt=AbstractPlus ]\nPurcell RH et al. (2018) Adhesion G Protein‐Coupled Receptors as Drug Targets.  Annu Rev Pharmacol Toxicol \n 58 : 429‐449 [ https://www.ncbi.nlm.nih.gov/pubmed/28968187?dopt=AbstractPlus ]\n\nThe nomenclature of the Adrenoceptors has been agreed by the \n NC‐IUPHAR  Subcommittee on Adrenoceptors [ http://www.ncbi.nlm.nih.gov/pubmed/7938162?dopt=AbstractPlus ],  see also  [ http://www.ncbi.nlm.nih.gov/pubmed/7568329?dopt=AbstractPlus ].\nα 1 ‐Adrenoceptors are activated by the endogenous agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  and (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 .  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=485 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=483  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=515  are agonists and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=515  antagonists considered selective for α 1 ‐ relative to α 2 ‐adrenoceptors. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5385  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=482  (BE2254) are relatively selective radioligands.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=487  also has high affinity for L‐type Ca 2+  channels. Fluorescent derivatives of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  (Bodipy PLprazosin‐ QAPB) are used to examine cellular localisation of α 1 ‐adrenoceptors. Selective α 1 ‐adrenoceptor agonists are used as nasal decongestants; antagonists to treat hypertension ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7170 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7170 ) and benign prostatic hyperplasia ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7109 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=488 ). The α 1 ‐ and β 2 ‐adrenoceptor antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=551  is used to treat congestive heart failure, although the contribution of α 1 ‐adrenoceptor blockade to the therapeutic effect is unclear. Several anti‐depressants and anti‐psychotic drugs are α 1 ‐adrenoceptor antagonists contributing to side effects such as orthostatic hypotension and extrapyramidal effects.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=22 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=23 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=24 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:277 ,  http://www.uniprot.org/uniprot/P35348 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:278 ,  http://www.uniprot.org/uniprot/P35368 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:280 ,  http://www.uniprot.org/uniprot/P25100 \n Endogenous agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  [ http://www.ncbi.nlm.nih.gov/pubmed/8564227?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10433504?dopt=AbstractPlus ] – (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  [ http://www.ncbi.nlm.nih.gov/pubmed/8564227?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=124  [ http://www.ncbi.nlm.nih.gov/pubmed/8564227?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8719417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10433504?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=485  [ http://www.ncbi.nlm.nih.gov/pubmed/10433504?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=483 [ http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10433504?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=485  [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7969082?dopt=AbstractPlus ] – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=480  [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7616455?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3469  [ http://www.ncbi.nlm.nih.gov/pubmed/14678390?dopt=AbstractPlus ] – – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  (Inverse agonist) (p K \n i  9–9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9490024?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10334511?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7170  (p K \n i  9.3) [ 0795 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7302  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9379432?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=502  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7109  (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10812954?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  (Inverse agonist) (p K \n i  9.6–9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=488  (Inverse agonist) (p K \n i  9.5–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7170  (p K \n i  9.1) [ 0795 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7109  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/7658428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7302  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9379432?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=502  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  (Inverse agonist) (p K \n i  9.5–10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=488  (p K \n i  9.8–10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7170  (p K i 9.1) [ 0795 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7302  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9379432?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7109  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10812954?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7155  (p K \n i  8.4) [ 0079 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=502  (Inverse agonist) (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7381  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7207  (p K \n i  6.6) [ 0079 ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=488  (p K \n i  10–10.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9490024?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10334511?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=493  (p K \n i  10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=487  (p K \n i  9.1–10) [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7651358?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7381  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10369480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=498  (p K \n i  8.8–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10812954?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190863?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7752182?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6663 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6663  (p K \n i  9.2–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/23935897?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20015090?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=495  (p K \n i  9.2–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9490024?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9490024?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8632751?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8459  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9190864?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=506  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9548811?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8461  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8764344?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9  (p K \n i  8.7–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/11354357?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11459121?dopt=AbstractPlus ]\nThe α 1C ‐adrenoceptor corresponds to the pharmacologically defined α 1A ‐adrenoceptor [ http://www.ncbi.nlm.nih.gov/pubmed/7568329?dopt=AbstractPlus ]. Some tissues possess α 1A ‐adrenoceptors (α 1L ‐adrenoceptors [ http://www.ncbi.nlm.nih.gov/pubmed/9249248?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17162094?dopt=AbstractPlus ]) that display relatively low affinity in functional and binding assays for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  indicative of different receptor states or locations. α1A‐adrenoceptor C‐terminal splice variants form homo‐ and heterodimers, but fail to generate a functional α 1L ‐adrenoceptor [ http://www.ncbi.nlm.nih.gov/pubmed/15266013?dopt=AbstractPlus ]. α 1D ‐Adrenoceptors form heterodimers with α 1B ‐ or β 2 ‐adrenoceptors that show increased cell‐surface expression [ http://www.ncbi.nlm.nih.gov/pubmed/15615865?dopt=AbstractPlus ]. Recombinant α 1D ‐adrenoceptors have been shown in some heterologous systems to be mainly located intracellularly but cell‐surface localization is encouraged by truncation of the Nterminus, or by co‐expression of α 1B ‐ or β 2 ‐adrenoceptors [ http://www.ncbi.nlm.nih.gov/pubmed/14718583?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14718583?dopt=AbstractPlus ]. In blood vessels all three α 1 ‐adrenoceptor subtypes are located on the surface and intracellularly [ http://www.ncbi.nlm.nih.gov/pubmed/19572943?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19888965?dopt=AbstractPlus ]. Signalling is predominantly via G q/11  butα1‐adrenoceptors also couple toG i/o , G s  and G 12/13 . Several α 1A ‐adrenoceptor agonists display ligand directed signalling bias relative to noradrenaline [ http://www.ncbi.nlm.nih.gov/pubmed/20978120?dopt=AbstractPlus ]. There are also differences between subtypes in coupling efficiency to different pathways. In vascular smooth muscle, the potency of agonists is related to the predominant subtype, α 1D ‐ conveying greater agonist sensitivity than α 1A ‐adrenoceptors [ http://www.ncbi.nlm.nih.gov/pubmed/23373597?dopt=AbstractPlus ].\nα 2 ‐Adrenoceptors are activated by (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  and with lower potency by (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 .  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=520  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5442  are agonists and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=136  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=102  antagonists selective for α 2 ‐ relative to α 1 ‐adrenoceptors. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=223 , [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5386  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=528  are relatively selective radioligands. There is species variation in the pharmacology of the α 2A ‐adrenoceptor. Multiple mutations of α 2 ‐adrenoceptors have been described, some associated with alterations in function. Presynaptic α 2 ‐adrenoceptors regulate many functions in the nervous system. The α 2 ‐adrenoceptor agonists  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=516 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5443  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=520  affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=516  is an anti‐hypertensive and counteracts opioid withdrawal.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=521  (also  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=523 ) is used as a sedative and analgesic in human and veterinary medicine with sympatholytic and anxiolytic properties. The α 2 ‐adrenoceptor antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=102  has been used to treat erectile dysfunction and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7241  as an anti‐depressant. The α 2B  subtype appears to be involved in neurotransmission in the spinal cord and α 2C  in regulating catecholamine release from adrenal chromaffin cells.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=25 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=26 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=27 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:281 ,  http://www.uniprot.org/uniprot/P08913 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:282 ,  http://www.uniprot.org/uniprot/P18089 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:283 ,  http://www.uniprot.org/uniprot/P18825 \n Endogenous agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ] (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ] (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=521  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9227000?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=516  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=520 [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9227000?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7117  [ http://www.ncbi.nlm.nih.gov/pubmed/8784451?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5443  [ 0079 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=522  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9283709?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=521  [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9227000?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=516  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=520  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5443  [ 0079 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=522 [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=521  [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9760042?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=520  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9227000?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9824686?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7117  [ http://www.ncbi.nlm.nih.gov/pubmed/8784451?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=522  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5443  [ 0079 ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=124  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9227000?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ] – – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=102  (p K \n i  8.4–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/1353247?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7908642?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=102  (p K \n i  7.9–8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/1353247?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7908642?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7268  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1834671?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7310  (p K \n i  5.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=102  (p K \n i  8.5–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1353247?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7908642?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=499  (p K i 8.4–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/1353247?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=53  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7241  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/15771415?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7310  (p K \n i  5.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9605427?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=525  (p K \n i  8.2–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2573535?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3470  (p K \n i  7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/1970500?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3930  (p K \n B  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/17220913?dopt=AbstractPlus ] Labelled ligands – – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=527  (Antagonist) (p K \n d  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/7996470?dopt=AbstractPlus ]\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=524  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  show selectivity for α 2B ‐ and α 2C ‐adrenoceptors over α 2A ‐adrenoceptors. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=124  is a reduced efficacy imidazoline agonist but also binds to non‐GPCR binding sites for imidazolines, classified as I 1 , I 2  and I 3  sites [ http://www.ncbi.nlm.nih.gov/pubmed/15224384?dopt=AbstractPlus ]; catecholamines have a low affinity, while rilmenidine and moxonidine are selective ligands evoking hypotensive effects  in vivo . I 1 ‐imidazoline receptors cause central inhibition of sympathetic tone, I 2 ‐imidazoline receptors are an allosteric binding site on monoamine oxidase B, and I 3 ‐imidazoline receptors regulate insulin secretion from pancreatic β‐cells. α 2A ‐adrenoceptor stimulation reduces insulin secretion from β‐islets [ http://www.ncbi.nlm.nih.gov/pubmed/22645144?dopt=AbstractPlus ], with a polymorphism in the 5’‐UTR of the ADRA2A gene being associated with increased receptor expression in β‐islets and heightened susceptibility to diabetes [ http://www.ncbi.nlm.nih.gov/pubmed/19965390?dopt=AbstractPlus ]. α 2A ‐ and α 2C ‐adrenoceptors form homodimers [ http://www.ncbi.nlm.nih.gov/pubmed/16605244?dopt=AbstractPlus ]. Heterodimers between α 2A ‐ and either the α 2C ‐adrenoceptor or  μ  opioid peptide receptor exhibit altered signalling and trafficking properties compared to the individual receptors [ http://www.ncbi.nlm.nih.gov/pubmed/16605244?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19126537?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18193048?dopt=AbstractPlus ]. Signalling by α 2 ‐adrenoceptors is primarily via G i/o , although the α 2A ‐adrenoceptor also couples to Gs [ http://www.ncbi.nlm.nih.gov/pubmed/7559592?dopt=AbstractPlus ]. Imidazoline compounds display bias relative to each other at the α 2A ‐adrenoceptor [ http://www.ncbi.nlm.nih.gov/pubmed/12649300?dopt=AbstractPlus ]. The noradrenaline reuptake inhibitor desipramine acts directly on the α 2A ‐adrenoceptor to promote internalisation  via  recruitment of arrestin [ http://www.ncbi.nlm.nih.gov/pubmed/21859713?dopt=AbstractPlus ].\nβ‐Adrenoceptors are activated by the endogenous agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  and (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 . Isoprenaline is selective for β‐adrenoceptors relative to α 1 ‐ and α 2 ‐adrenoceptors, while  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=564  (p K i 8.2‐9.2) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=132  (p K i 10.011.0) are relatively β 1  and β 2  adrenoceptor‐selective antagonists. (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=538  and (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5571  show selectivity for β 1 ‐ relative to β 2 ‐adrenoceptors. Pharmacological differences exist between human and mouse β 3 ‐adrenoceptors, and the ’rodent selective’ agonists  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=567  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3462  have low efficacy at the human β 3 ‐adrenoceptor whereas  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=532  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3931  activate human β 3 ‐adrenoceptors [88]. β 3 ‐Adrenoceptors are resistant to blockade by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=564 , but can be blocked by high concentrations of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=550 .  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=547  has reasonably high affinity at β 3 ‐adrenoceptors, but does not discriminate well between the three β‐ subtypes whereas  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3931  is more selective. [ 125 I]‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=132 , [ 125 I]‐hydroxy benzylpindolol and [ 3 H]‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=563  are high affinity radioligands that label β 1 ‐ and β 2 ‐ adrenoceptors and β 3 ‐adrenoceptors can be labelled with higher concentrations (nM) of [ 125 I]‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=132  together with β 1 ‐ and β 2 ‐adrenoceptor antagonists. [ 3 H]‐L748337 is a β 3 ‐selective radioligand [ http://www.ncbi.nlm.nih.gov/pubmed/24183974?dopt=AbstractPlus ]. Fluorescent ligands such as BODIPY‐TMR‐ CGP12177  can be used to track βadrenoceptors at the cellular level [8]. Somewhat selective β 1 adrenoceptor agonists ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=534 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=535 ) are used short term to treat cardiogenic shock but, chronically, reduce survival. β 1 ‐Adrenoceptor‐preferring antagonists areused totreathypertension ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=548 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=549 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7129 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=553  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7246 ), cardiac arrhythmias ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=548 , bisoprolol,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7178 ) and cardiac failure ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=553 , nebivolol). Cardiac failure is also treated with carvedilol that blocks β 1 ‐ and β 2 ‐adrenoceptors, as well as α 1 ‐adrenoceptors. Short ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=558 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=560 ) and long ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3465 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=559 ) acting β 2 ‐adrenoceptor‐selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation β‐adrenoceptor antagonists ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=564 ) block both β 1 ‐ and β 2 ‐adrenoceptors and there are no β 2 adrenoceptor‐selective antagonists used therapeutically. The β 3 ‐adrenoceptor agonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7445  is used to control overactive bladder syndrome.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=28 ‐ http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=28 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=29 ‐ http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=29 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=30 ‐ http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=30 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:285 ,  http://www.uniprot.org/uniprot/P08588 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:286 ,  http://www.uniprot.org/uniprot/P07550 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:288 ,  http://www.uniprot.org/uniprot/P13945 \n Potency order of endogenous ligands (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  > (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 \n (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  > (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 \n (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  = (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 \n Endogenous agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  [ http://www.ncbi.nlm.nih.gov/pubmed/2849109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=484 ] (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479  [ http://www.ncbi.nlm.nih.gov/pubmed/2849109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9295336?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505 ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ] (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=505  [ http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14744619?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9131260?dopt=AbstractPlus ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479 ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=91  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17804228?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=536  [ http://www.ncbi.nlm.nih.gov/pubmed/2849109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8982677?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=535  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=91  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17804228?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7479  [ http://www.ncbi.nlm.nih.gov/pubmed/15324892?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=536  [ http://www.ncbi.nlm.nih.gov/pubmed/8982677?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=556  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9295336?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=569  [ http://www.ncbi.nlm.nih.gov/pubmed/8719421?dopt=AbstractPlus ] Selective agonists (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5571  [ http://www.ncbi.nlm.nih.gov/pubmed/9117106?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=538  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=534  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7902433?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3465  [ http://www.ncbi.nlm.nih.gov/pubmed/20590599?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=559 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3466 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7353  [ http://www.ncbi.nlm.nih.gov/pubmed/20462258?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3464 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7455  [ http://www.ncbi.nlm.nih.gov/pubmed/22932315?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=557  [ http://www.ncbi.nlm.nih.gov/pubmed/24454993?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=558  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=560  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7250  [ http://www.ncbi.nlm.nih.gov/pubmed/19168263?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3931  [ http://www.ncbi.nlm.nih.gov/pubmed/20590599?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3467  [ http://www.ncbi.nlm.nih.gov/pubmed/9873496?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7445  [ http://www.ncbi.nlm.nih.gov/pubmed/17293563?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=532  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7903415?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8719421?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9117106?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3468  [ http://www.ncbi.nlm.nih.gov/pubmed/11959793?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=567 [ http://www.ncbi.nlm.nih.gov/pubmed/7903415?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7912272?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8719421?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3462  [ http://www.ncbi.nlm.nih.gov/pubmed/11249148?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=551  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=550  (p K \n i  7.3–9) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=547  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=570  (p K \n i  8.4) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7207  (p K \n i  8.2) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=553  (p K \n i  7–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7178  (p K \n i  6.9) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=554  (p K \n i  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=555  (p K \n i  6.1–6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2561  (p K \n i  6.7) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7297  (p K \n i  6.1) [79] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=551  (p K \n i  9.4–9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=565  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=564  (p K \n i  9.1–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12920204?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=547  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=570  (p K \n i  9.3) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=550  (p K \n i  8.3–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=563  (p K i 9) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=554  (p K \n i  7–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7207  (p K \n i  8) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2561  (p K \n i  7.4) [79],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7297  (p K \n i  6.5) [79] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=547  (p K \n i  6.9–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8730727?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14730417?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=550  (p K \n i  6.8–7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7903415?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8719421?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=564  (p K i 6.3–7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14744619?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=570  (p K \n i  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/14744619?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=541  (p K \n i  8.5–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8035  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/11572462?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=549  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7246  (pIC 50  8.1–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/2462161?dopt=AbstractPlus ] – Rabbit,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=548  (p K \n i  6.7–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15060759?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15060759?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7107  (p K \n i  6.4) [79] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=543  (Inverse agonist) (p K \n i  9.2–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/15655528?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12920204?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3932  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3463  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10411574?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=562  (Antagonist) (p K \n d  10.4–11.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10531390?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8982677?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=562  (Antagonist) (p K \n d  11.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8982677?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=562  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10079020?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9117106?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14744619?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8982677?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9131260?dopt=AbstractPlus ] Comments The agonists indicated have less than two orders of magnitude selectivity [ http://www.ncbi.nlm.nih.gov/pubmed/20590599?dopt=AbstractPlus ]. – Agonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3468  has a pEC50 of 6.9 for the splice variant of the mouse β 3  receptor, β 3b  [ http://www.ncbi.nlm.nih.gov/pubmed/11959793?dopt=AbstractPlus ].\n[ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=562  can be used to define β 1 ‐ or β 2 adrenoceptors when conducted in the presence of a β 1 ‐ or β 2 adrenoceptor‐selective antagonist. A fluorescent analogue of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=532  can be used to study β 2 ‐adrenoceptors in living cells [ http://www.ncbi.nlm.nih.gov/pubmed/12770928?dopt=AbstractPlus ]. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=562  at higher (nM) concentrations can be used to label β 3 ‐adrenoceptors in systems with few if any other β‐adrenoceptor subtypes. The β 3 ‐adrenoceptor has an intron in the coding region, but splice variants have only been described for the mouse [ http://www.ncbi.nlm.nih.gov/pubmed/10455305?dopt=AbstractPlus ], where the isoforms display different signalling characteristics [ http://www.ncbi.nlm.nih.gov/pubmed/11959793?dopt=AbstractPlus ]. There are 3 β‐adrenoceptors in turkey (termed the tβ, tβ3c and tβ4c) that have a pharmacology that differs from the human β‐adrenoceptors [ http://www.ncbi.nlm.nih.gov/pubmed/21152092?dopt=AbstractPlus ]. Numerous polymorphisms have been described for the β‐adrenoceptors; some are associated with signalling and trafficking, altered susceptibility to disease and/or altered responses to pharmacotherapy [ http://www.ncbi.nlm.nih.gov/pubmed/15090197?dopt=AbstractPlus ]. All β‐adrenoceptors couple to G s  (activating adenylyl cyclase and elevating cAMP levels), but also activate G i  and β‐arrestin‐mediated signalling. Many β 1 ‐ and β 2 ‐adrenoceptor antagonists are agonists at β 3 adrenoceptors ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3462  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=569 ). Many ‘antagonists’ of cAMP accumulation, for example  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=551  and bucindolol, weakly activate MAP kinase pathways [ http://www.ncbi.nlm.nih.gov/pubmed/14645666?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20132209?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16901982?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18403719?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17717109?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18684840?dopt=AbstractPlus ] and thus display ’protean agonism’.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=550  acts as a neutral antagonist in most systems so far examined. Agonists also display biased signalling at the β 2 ‐adrenoceptor via G s  or arrestins [ http://www.ncbi.nlm.nih.gov/pubmed/18086673?dopt=AbstractPlus ]. X‐ray crystal structures have been described of the agonist bound [ http://www.ncbi.nlm.nih.gov/pubmed/21228877?dopt=AbstractPlus ] and antagonist bound forms of the β 1 [ http://www.ncbi.nlm.nih.gov/pubmed/18594507?dopt=AbstractPlus ], agonist‐bound [ http://www.ncbi.nlm.nih.gov/pubmed/17962520?dopt=AbstractPlus ] and antagonist‐bound forms of the β 2 ‐adrenoceptor [ http://www.ncbi.nlm.nih.gov/pubmed/21228869?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21228876?dopt=AbstractPlus ], as well as a fully active agonistbound, G s  protein‐coupled β2‐adrenoceptor [ http://www.ncbi.nlm.nih.gov/pubmed/21772288?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=551  and bucindolol bind to a site on the β1‐adrenoceptor involving contacts in TM2, 3, and 7 and extracellular loop 2 that may facilitate coupling to arrestins [ http://www.ncbi.nlm.nih.gov/pubmed/18594507?dopt=AbstractPlus ]. Compounds displaying arrestinbiased signalling at the β2‐adrenoceptor have a greater effect on the conformation of TM7, whereas full agonists for G s  coupling promote movement of TM5 and TM6 [ http://www.ncbi.nlm.nih.gov/pubmed/22267580?dopt=AbstractPlus ]. Recent studies using NMR spectroscopy demonstrate significant conformational flexibility in the β 2 ‐adrenoceptor that is stabilized by both agonist and G proteins highlighting the dynamic nature of interactions with both ligand and downstreamsignalling partners [ http://www.ncbi.nlm.nih.gov/pubmed/23721409?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25981665?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23374348?dopt=AbstractPlus ]. Such flexibility likely has consequences for our understanding of biased agonism, and for the future therapeutic exploitation of this phenomenon.\nBaker JG et al. (2011) Evolution of β‐blockers: from anti‐anginal drugs to ligand‐directed signalling.  Trends Pharmacol. Sci. \n 32 : 227‐34 [ https://www.ncbi.nlm.nih.gov/pubmed/21429598?dopt=AbstractPlus ]\nBylund DB et al. (1994) International Union of Pharmacology nomenclature of adrenoceptors.  Pharmacol. Rev. \n 46 : 121‐136 [ https://www.ncbi.nlm.nih.gov/pubmed/7938162?dopt=AbstractPlus ]\nEvans BA et al. (2010) Ligand‐directed signalling at beta‐adrenoceptors.  Br. J. Pharmacol. \n 159 : 1022‐38 [ https://www.ncbi.nlm.nih.gov/pubmed/20132209?dopt=AbstractPlus ]\nJensen BC et al. (2011) Alpha‐1‐adrenergic receptors: targets for agonist drugs to treat heart failure.  J. Mol. Cell. Cardiol. \n 51 : 518‐28 [ https://www.ncbi.nlm.nih.gov/pubmed/21118696?dopt=AbstractPlus ]\nKobilka BK. (2011) Structural insights into adrenergic receptor function and pharmacology.  Trends Pharmacol. Sci. \n 32 : 213‐8 [ https://www.ncbi.nlm.nih.gov/pubmed/21414670?dopt=AbstractPlus ]\nLanger SZ. (2015) a2‐Adrenoceptors in the treatment of major neuropsychiatric disorders.  Trends Pharmacol. Sci. \n 36 : 196‐202 [ https://www.ncbi.nlm.nih.gov/pubmed/25771972?dopt=AbstractPlus ]\nMichel MC et al. (2015) Selectivity of pharmacological tools: implications for use in cell physiology. A review in the theme: Cell signaling: proteins, pathways and mechanisms.  Am. J. Physiol., Cell Physiol. \n 308 : C505‐20 [ https://www.ncbi.nlm.nih.gov/pubmed/25631871?dopt=AbstractPlus ]\n\nThe actions of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) (Ang II) are mediated by AT 1  and AT 2  receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Angiotensin receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/10977869?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26315714?dopt=AbstractPlus ]), which have around 30% sequence similarity. The decapeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=583 ,  http://www.uniprot.org/uniprot/P01019 ), the octapeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2504 ,  http://www.uniprot.org/uniprot/P01019 ) and the heptapeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=585 ,  http://www.uniprot.org/uniprot/P01019 ) are endogenous ligands.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=590 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=587 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=592 , etc. are clinically used AT 1  receptor blockers.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=34 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=35 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:336 ,  http://www.uniprot.org/uniprot/P30556 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:338 ,  http://www.uniprot.org/uniprot/P50052 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) [466,  http://www.ncbi.nlm.nih.gov/pubmed/10193788?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=585 ,  http://www.uniprot.org/uniprot/P01019 ) [466],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5368 ,  http://www.uniprot.org/uniprot/P01019 ) (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12006574?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=585  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8242249?dopt=AbstractPlus , 466,  http://www.ncbi.nlm.nih.gov/pubmed/2775266?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2504 ,  http://www.uniprot.org/uniprot/P01019 ) [466,  http://www.ncbi.nlm.nih.gov/pubmed/7850406?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2775266?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=582 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) [ http://www.ncbi.nlm.nih.gov/pubmed/21542804?dopt=AbstractPlus ] Agonists [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6903 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6903 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6903  [ http://www.ncbi.nlm.nih.gov/pubmed/11901215?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10066768?dopt=AbstractPlus ] – Rat – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3936  [ http://www.ncbi.nlm.nih.gov/pubmed/7829475?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6895  [ http://www.ncbi.nlm.nih.gov/pubmed/9383393?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3944  [ http://www.ncbi.nlm.nih.gov/pubmed/21542804?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=595  [466,  http://www.ncbi.nlm.nih.gov/pubmed/2194459?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6918  [ http://www.ncbi.nlm.nih.gov/pubmed/22802221?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6899  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/7853190?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6913  (pIC 50  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/22410249?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6917  (pIC 50  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/22889560?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6910  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11303957?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6902  (p K \n d  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/20801892?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=598  (pIC 50  9) [ http://www.ncbi.nlm.nih.gov/pubmed/2590220?dopt=AbstractPlus ] – Rat Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=587  (pIC 50  9.5–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/10193788?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=588  (pIC 50  8.4–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/1309870?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=590  (pIC 50  7.4–8.7) [466,  http://www.ncbi.nlm.nih.gov/pubmed/8372104?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=592  (pIC 50  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9878991?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=591  (pIC 50  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/11451212?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=596  (pIC 50  8.5–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/2314387?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2590220?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8469774?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8374  (pIC 50  8.5–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/24507378?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24507377?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23489258?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=597  (p K \n d  8.7–9.2) [466,  http://www.ncbi.nlm.nih.gov/pubmed/2402226?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1709220?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6907  (Antagonist) (p K \n d  10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10079018?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6897 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6897  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7759541?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7759541?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3940  (Antagonist) (p K \n d  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8463997?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3941  (Antagonist) (p K \n d  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8282008?dopt=AbstractPlus ] – Rat [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=594  (Agonist) [466,  http://www.ncbi.nlm.nih.gov/pubmed/2775266?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1764088?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6906  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10024318?dopt=AbstractPlus ] – Rat Comments \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=592  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=587  are also reported to be agonists of PPARγ [ http://www.ncbi.nlm.nih.gov/pubmed/19021699?dopt=AbstractPlus ]. –\nAT 1  receptors are predominantly coupled to G q/11 , however they are also linked to arrestin recruitment and stimulate G protein‐independent arrestin signalling [ http://www.ncbi.nlm.nih.gov/pubmed/20427692?dopt=AbstractPlus ]. Most species express a single  AGTR1  gene, but two related  agtr1a  and a gtr1b  receptor genes are expressed in rodents. The AT 2  receptor counteracts several of the growth responses initiated by the AT 1  receptors. The AT 2  receptor is much less abundant than the AT 1  receptor in adult tissues and is upregulated in pathological conditions. AT 1  receptor antagonists bearing substituted 4‐phenylquinoline moieties have been synthesized, which bind to AT 1  receptors with nanomolar affinity and are slightly more potent than  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=590  in functional studies [ http://www.ncbi.nlm.nih.gov/pubmed/15115399?dopt=AbstractPlus ]. The antagonist activity of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3944  at the AT 2  receptor has also been reported [ http://www.ncbi.nlm.nih.gov/pubmed/3071214?dopt=AbstractPlus ]. The AT 1  and bradykinin B 2  receptors have been proposed to form a heterodimeric complex [ http://www.ncbi.nlm.nih.gov/pubmed/10993080?dopt=AbstractPlus ] .  β‐Arrestin1 prevents AT 1 ‐B 2  receptor heteromerization[ http://www.ncbi.nlm.nih.gov/pubmed/30503206?dopt=AbstractPlus ]. There is also evidence for an AT 4  receptor that specifically binds  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5368  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:333 ,  http://www.uniprot.org/uniprot/P01019 ) and is located in the brain and kidney. An additional putative endogenous ligand for the AT4 receptor has been described ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5353  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4827 ,  http://www.uniprot.org/uniprot/P68871 ), a globin decapeptide) [ http://www.ncbi.nlm.nih.gov/pubmed/9166749?dopt=AbstractPlus ].\nAsada H  et al . (2018) Crystal structure of the human angiotensin II type 2 receptor bound to an angiotensin II analog.  Nat. Struct. Mol. Biol. \n 25 : 570‐576 [ https://www.ncbi.nlm.nih.gov/pubmed/29967536?dopt=AbstractPlus ]\nKarnik SS  et al . (2015) International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].  Pharmacol. Rev. \n 67 : 754‐819 [ https://www.ncbi.nlm.nih.gov/pubmed/26315714?dopt=AbstractPlus ]\nSingh KD  et al . (2019) Mechanism of Hormone Peptide Activation of a GPCR: Angiotensin II Activated State of AT_1R Initiated by van der Waals Attraction.  J Chem Inf Model \n 59 : 373‐385 [ https://www.ncbi.nlm.nih.gov/pubmed/30608150?dopt=AbstractPlus ]\nWingler LM  et al . (2019) Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations.  Cell \n 176 : 468‐478.e11 [ https://www.ncbi.nlm.nih.gov/pubmed/30639099?dopt=AbstractPlus ]\nWingler LM  et al . (2019) Distinctive Activation Mechanism for Angiotensin Receptor Revealed by a Synthetic Nanobody.  Cell \n 176 : 479‐490.e12 [ https://www.ncbi.nlm.nih.gov/pubmed/30639100?dopt=AbstractPlus ]\nZhang H  et al . (2015) Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.  Cell \n 161 : 833‐44 [ https://www.ncbi.nlm.nih.gov/pubmed/25913193?dopt=AbstractPlus ]\n\nThe apelin receptor ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the apelin receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/20605969?dopt=AbstractPlus ]) responds to apelin, a 36 amino‐acid peptide derived initially from bovine stomach.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=606  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=605 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) are the predominant endogenous ligands which are cleaved from a 77 amino‐acid precursor peptide ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 \n http://www.uniprot.org/uniprot/Q9ULZ1 ) by a so far unidentified enzymatic pathway [ http://www.ncbi.nlm.nih.gov/pubmed/9792798?dopt=AbstractPlus ]. A second family of peptides discovered independently and named Elabela [ http://www.ncbi.nlm.nih.gov/pubmed/24316148?dopt=AbstractPlus ] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [ http://www.ncbi.nlm.nih.gov/pubmed/24407481?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28137936?dopt=AbstractPlus ]. Structure‐activity relationship Elabela analogues have been described [ http://www.ncbi.nlm.nih.gov/pubmed/26986036?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=36 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:339 ,  http://www.uniprot.org/uniprot/P35414 \n Potency order of endogenous ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=605  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=606  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9792798?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=605  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10777510?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12603839?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7930  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:48925 ,  http://www.uniprot.org/uniprot/P0DMC3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/25995451?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3556  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15341513?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15341513?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=599  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11336787?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11336787?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8525  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:48925 ,  http://www.uniprot.org/uniprot/P0DMC3 )  [2378] ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8524  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:48925 ,  http://www.uniprot.org/uniprot/P0DMC3 )  [2378] ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=606  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16665 ,  http://www.uniprot.org/uniprot/Q9ULZ1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11336787?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12603839?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8526  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:48925 ,  http://www.uniprot.org/uniprot/Q9ULZ1 )  [2378] \n Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9448  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/27475715?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8523  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/25712721?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6186  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/21560248?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=603 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=603 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=603 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11336787?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3761 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3761 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3761  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10777510?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=601 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=601  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11250876?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=602  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=604 )[ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=604  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12603839?dopt=AbstractPlus ]\nPotency order determined for heterologously expressed human apelin receptor (p D \n 2  values range from 9.5 to 8.6). The apelin receptor may also act as a co‐receptor with CD4 for isolates of human immunodeficiency virus, with apelin blocking this function [ http://www.ncbi.nlm.nih.gov/pubmed/11090199?dopt=AbstractPlus ]. A modified apelin‐13 peptide,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5354 ) was reported to block the hypotensive response to apelin in rat  in vivo  [ http://www.ncbi.nlm.nih.gov/pubmed/15486224?dopt=AbstractPlus ], however, this peptide exhibits agonist activity in HEK293 cells stably expressing the recombinant apelin receptor [ http://www.ncbi.nlm.nih.gov/pubmed/12939143?dopt=AbstractPlus ]. The apelin receptor antagonist, MM54, was reported to suppress tumour growth and increase survival in an intracranial xenograft mouse model of glioblastoma [ http://www.ncbi.nlm.nih.gov/pubmed/29053791?dopt=AbstractPlus ].\nCheng B  et al . (2012) Neuroprotection of apelin and its signaling pathway.  Peptides \n 37 : 171‐3 [ https://www.ncbi.nlm.nih.gov/pubmed/22820556?dopt=AbstractPlus ]\nLangelaan DN  et al . (2009) Structural insight into G‐protein coupled receptor binding by apelin.  Biochemistry \n 48 : 537‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/19123778?dopt=AbstractPlus ]\nMughal A  et al . (2018) Vascular effects of apelin: Mechanisms and therapeutic potential.  Pharmacol. Ther. \n 190 : 139‐147 [ https://www.ncbi.nlm.nih.gov/pubmed/29807055?dopt=AbstractPlus ]\nO’Carroll AM  et al . (2013) The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis.  J. Endocrinol. \n 219 : R13‐35 [ https://www.ncbi.nlm.nih.gov/pubmed/23943882?dopt=AbstractPlus ]\nPitkin SL  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXIV. Apelin receptor nomenclature, distribution, pharmacology, and function.  Pharmacol. Rev. \n 62 : 331‐42 [ https://www.ncbi.nlm.nih.gov/pubmed/20605969?dopt=AbstractPlus ]\nYang P  et al . (2015) Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system.  Trends Pharmacol. Sci. \n 36 : 560‐7 [ https://www.ncbi.nlm.nih.gov/pubmed/26143239?dopt=AbstractPlus ]\n\nThe bile acid receptor (GPBA) responds to bile acids produced during the liver metabolism of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2718 . Selective agonists are promising drugs for the treatment of metabolic disorders, such as type II diabetes, obesity and atherosclerosis.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=37 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19680 ,  http://www.uniprot.org/uniprot/Q8TDU6 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=611  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=610  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=608 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=609  [ http://www.ncbi.nlm.nih.gov/pubmed/12524422?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12419312?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7048  [ http://www.ncbi.nlm.nih.gov/pubmed/20014870?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3945  [ http://www.ncbi.nlm.nih.gov/pubmed/19911773?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3306  [ http://www.ncbi.nlm.nih.gov/pubmed/17825251?dopt=AbstractPlus ]\nThe triterpenoid natural product  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3945  has also been reported to inhibit inflammatory signalling through the NF κ B pathway [ http://www.ncbi.nlm.nih.gov/pubmed/12960358?dopt=AbstractPlus ]. Disruption of GPBA expression is reported to protect from cholesterol gallstone formation [ http://www.ncbi.nlm.nih.gov/pubmed/16724960?dopt=AbstractPlus ]. A new series of 5‐phenoxy‐1,3‐dimethyl‐1H‐pyrazole‐4‐carboxamides have been reported as highly potent agonists [ http://www.ncbi.nlm.nih.gov/pubmed/23337601?dopt=AbstractPlus ].\nDuboc H  et al . (2014) The bile acid TGR5 membrane receptor: from basic research to clinical application.  Dig Liver Dis \n 46 : 302‐12 [ https://www.ncbi.nlm.nih.gov/pubmed/24411485?dopt=AbstractPlus ]\nLieu T  et al . (2014) GPBA: a GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation.  Br. J. Pharmacol. \n 171 : 1156‐66 [ https://www.ncbi.nlm.nih.gov/pubmed/24111923?dopt=AbstractPlus ]\nLefebvre P  et al . (2009) Role of bile acids and bile acid receptors in metabolic regulation.  Physiol. Rev. \n 89 : 147‐91 [ https://www.ncbi.nlm.nih.gov/pubmed/19126757?dopt=AbstractPlus ]\nvan Nierop FS  et al . (2017) Clinical relevance of the bile acid receptor TGR5 in metabolism.  Lancet Diabetes Endocrinol \n 5 : 224‐233 [ https://www.ncbi.nlm.nih.gov/pubmed/27639537?dopt=AbstractPlus ]\n\nMammalian bombesin (Bn) receptors comprise 3 subtypes: BB 1 , BB 2 , BB 3  ( nomenclature recommended by the NC‐IUPHAR Subcommittee on bombesin receptors , [ http://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ]). BB 1  and BB 2  are activated by the endogenous ligands  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=612  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4605 ,  http://www.uniprot.org/uniprot/P07492 ) (GRP),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=613  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7842 ,  http://www.uniprot.org/uniprot/P08949 ) (NMB) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3582 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4605 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4605 ).  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=616  is a tetradecapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the G q/11  and G 12 /13 family of G proteins [ http://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ]. Each of these receptors is widely distributed in the CNS and peripheral tissues [ http://www.ncbi.nlm.nih.gov/pubmed/26066663?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15726424?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25976083?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15203211?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22911445?dopt=AbstractPlus ]. Activation of BB 1  and BB 2  receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smoothmuscle contraction, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm and mediation of pruritus [ http://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ,  991 ,  992 ,  http://www.ncbi.nlm.nih.gov/pubmed/21042212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15134870?dopt=AbstractPlus , http://www.ncbi.nlm.nih.gov/pubmed/25976083?dopt=AbstractPlus ]. A physiological role for the BB 3  receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [ http://www.ncbi.nlm.nih.gov/pubmed/26066663?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22157398?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9367152?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27055378?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=38 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=38 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=39 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=39 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=40 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=40 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7843 ,  http://www.uniprot.org/uniprot/P28336 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4609 ,  http://www.uniprot.org/uniprot/P30550 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1113 ,  http://www.uniprot.org/uniprot/P32247 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=613  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7842 ,  http://www.uniprot.org/uniprot/P08949 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25976083?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21729729?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6178  [ http://www.ncbi.nlm.nih.gov/pubmed/21729729?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6175 ] – Selective agonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8509  [ http://www.ncbi.nlm.nih.gov/pubmed/24412111?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8502  [ http://www.ncbi.nlm.nih.gov/pubmed/24900461?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6170  [ http://www.ncbi.nlm.nih.gov/pubmed/23892571?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24900253?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15102928?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8507  [ http://www.ncbi.nlm.nih.gov/pubmed/25497965?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6188  [ http://www.ncbi.nlm.nih.gov/pubmed/20096642?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8504  [ http://www.ncbi.nlm.nih.gov/pubmed/20167483?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=635  (pIC 50  6.2–6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=626  (pIC 50  9.3–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=621  (pIC 50  9.3–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3871 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3871 \n [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3840 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3840 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3840 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3840 ) (p K \n i  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3889  (pIC 50  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11463790?dopt=AbstractPlus ] – Mouse, [( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 ‐( (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8446610?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=624  (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10231715?dopt=AbstractPlus ] – Mouse, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6183 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6183 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6183 ) (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/19463875?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6176  (pIC 50  8.6–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/20096642?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23892571?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8505  (pIC 50  5.3) [ http://www.ncbi.nlm.nih.gov/pubmed/25554218?dopt=AbstractPlus ]  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=627 ) Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3771 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=623 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=623  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=628 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=628  (Selective Antagonist) (p K \n d  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7684815?dopt=AbstractPlus ] – Mouse, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=623 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=623  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7838118?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3788 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8506  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/20096642?dopt=AbstractPlus ] – Mouse, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=631 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9325344?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23892571?dopt=AbstractPlus ]\nAll three human subtypes may be activated by [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=632 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9325344?dopt=AbstractPlus ]. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3946 ) has more than 200‐fold selectivity for BB 3  receptors over BB 1  and BB 2  [ http://www.ncbi.nlm.nih.gov/pubmed/15102928?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15102928?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25976083?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26524625?dopt=AbstractPlus ].\nGonzález N  et al . (2015) Bombesin receptor subtype 3 as a potential target for obesity and diabetes.  Expert Opin. Ther. Targets \n 19 : 1153‐70 [ https://www.ncbi.nlm.nih.gov/pubmed/26066663?dopt=AbstractPlus ]\nJensen RT  et al . (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states.  Pharmacol. Rev. \n 60 : 1‐42 [ https://www.ncbi.nlm.nih.gov/pubmed/18055507?dopt=AbstractPlus ]\nMaina T  et al . (2017) Theranostic Prospects of Gastrin‐Releasing Peptide Receptor‐Radioantagonists in Oncology.  PET Clin \n 12 : 297‐309 [ https://www.ncbi.nlm.nih.gov/pubmed/28576168?dopt=AbstractPlus ]\nMoreno P  et al . (2016) Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment.  Expert Opin. Ther. Targets \n 20 : 1055‐73 [ https://www.ncbi.nlm.nih.gov/pubmed/26981612?dopt=AbstractPlus ]\nQu X  et al . (2018) Recent insights into biological functions of mammalian bombesin‐like peptides and their receptors.  Curr Opin Endocrinol Diabetes Obes \n 25 : 36‐41 [ https://www.ncbi.nlm.nih.gov/pubmed/29120926?dopt=AbstractPlus ]\nRamos‐Álvarez I  et al . (2015) Insights into bombesin receptors and ligands: Highlighting recent advances.  Peptides \n 72 : 128‐44 [ https://www.ncbi.nlm.nih.gov/pubmed/25976083?dopt=AbstractPlus ]\n\nBradykinin (or kinin) receptors ( nomenclature as agreed by the  NC‐IUPHAR  subcommittee on Bradykinin (kinin) Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/15734727?dopt=AbstractPlus ]) are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=649  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ,  http://www.uniprot.org/uniprot/P01042 ) (BK), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ), Lys‐BK ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=650 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 )), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ), [Phospho‐Ser6]‐Bradykinin,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=639 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) (Ile‐SerBK), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3578 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3578 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3580 ]‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3580 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ). Variation in pharmacology and activity of B 1  and B 2  receptor antagonists at species orthologs has been documented.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=667  (Hoe140, Firazir) is approved in North America and Europe for the treatment of acute attacks of hereditary angioedema.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=41 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=41 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=42 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=42 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1029 ,  http://www.uniprot.org/uniprot/P46663 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1030 ,  http://www.uniprot.org/uniprot/P30411 \n Potency order of endogenous ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ,  http://www.uniprot.org/uniprot/P01042 ) > [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=650 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=649 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=650  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ,  http://www.uniprot.org/uniprot/P01042 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=649 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=646 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ) Endogenous agonists [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=644  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ,  http://www.uniprot.org/uniprot/P01042 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9111052?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9313952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8735629?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10422787?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=649  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6383 ,  http://www.uniprot.org/uniprot/P01042 ) Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10254  [ http://www.ncbi.nlm.nih.gov/pubmed/26565554?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=643 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=643 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=643  [ http://www.ncbi.nlm.nih.gov/pubmed/10422787?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10255  [ http://www.ncbi.nlm.nih.gov/pubmed/19111586?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23362191?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3841 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3841 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3841 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3841 , [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3846 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3846 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3846 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3846 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3846 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=672 ,  http://www.ncbi.nlm.nih.gov/pubmed/19111586?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=655  (p K \n i  9.2–10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/16368899?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9650825?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=642 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=642 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=642  (p K \n i  9.1–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9111052?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9313952?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=662  (p K \n i  9.1–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/14747609?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3906  (p A \n 2  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/24361511?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=661  (p A \n 2  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8901831?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=667  (p K \n i  10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10514288?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=674  (p A \n 2  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9095082?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=679  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10596852?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3791  (p K \n d  10), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3825 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3825  (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3826 ][ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3826 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3826  (Antagonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3812 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9333122?dopt=AbstractPlus ] – Mouse, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3831  (Antagonist) (p K \n d  9.1–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9651119?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11379050?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3765 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3765  (Agonist)\nCampos MM  et al . (2006) Non‐peptide antagonists for kinin B1 receptors: new insights into their therapeutic potential for the management of inflammation and pain.  Trends Pharmacol. Sci. \n 27 : 646‐51 [ https://www.ncbi.nlm.nih.gov/pubmed/17056130?dopt=AbstractPlus ]\nDuchene J  et al . (2009) The kinin B(1) receptor and inflammation: new therapeutic target for cardiovascular disease.  Curr Opin Pharmacol \n 9 : 125‐31 [ https://www.ncbi.nlm.nih.gov/pubmed/19124274?dopt=AbstractPlus ]\nMarceau F  et al . (2004) Bradykinin receptor ligands: therapeutic perspectives.  Nat Rev Drug Discov \n 3 : 845‐52 [ https://www.ncbi.nlm.nih.gov/pubmed/15459675?dopt=AbstractPlus ]\nPaquet JL  et al . (1999) Pharmacological characterization of the bradykinin B2 receptor: inter‐species variability and dissociation between binding and functional responses.  Br. J. Pharmacol. \n 126 : 1083‐90 [ https://www.ncbi.nlm.nih.gov/pubmed/10204994?dopt=AbstractPlus ]\nThornton E  et al . (2010) Kinin receptor antagonists as potential neuroprotective agents in central nervous system injury.  Molecules \n 15 : 6598‐618 [ https://www.ncbi.nlm.nih.gov/pubmed/20877247?dopt=AbstractPlus ]\nWhalley ET  et al . (2012) Discovery and therapeutic potential of kinin receptor antagonists.  Expert Opin Drug Discov \n 7 : 1129‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/23095011?dopt=AbstractPlus ]\n\nThis receptor family comprises a group of receptors for the calcitonin/CGRP family of peptides. The calcitonin (CT), amylin (AMY), calcitonin gene‐related peptide (CGRP) and adrenomedullin (AM) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on CGRP, AM, AMY, and CT receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/18552275?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12037140?dopt=AbstractPlus ]) are generated by the genes  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1440  (which codes for the CT receptor) and  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16709  (which codes for the calcitonin receptor‐like receptor, CLR, previously known as CRLR). Their function and pharmacology are altered in the presence of RAMPs (receptor activity‐modifying proteins), which are single TM domain proteins of  ca.  130 amino acids, identified as a family of three members; RAMP1, RAMP2 and RAMP3. There are splice variants of the CT receptor; these in turn produce variants of the AMY receptor [ http://www.ncbi.nlm.nih.gov/pubmed/12037140?dopt=AbstractPlus ], some of which can be potently activated by CGRP. The endogenous agonists are the peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P01258 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681 ,  http://www.uniprot.org/uniprot/P06881 ) (formerly known as CGRP‐I),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) (formerly known as CGRP‐II),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) (occasionally called islet‐amyloid polypeptide, diabetes‐associated polypeptide),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ). There are species differences in peptide sequences, particularly for the CTs.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5369  {Pig} (CRSP) is another member of the family with selectivity for the CT receptor but it is not expressed in humans [ http://www.ncbi.nlm.nih.gov/pubmed/12556539?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=702  (also known as BIBN4096BS,  p Ki10.5) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=703  (also known as MK0974,  p Ki9) are the most selective antagonists available, showing selectivity for CGRP receptors, with a particular preference for those of primate origin. CLR (calcitonin receptor‐like receptor) by itself binds no known endogenous ligand, but in the presence of RAMPs it gives receptors for CGRP, adrenomedullin and adrenomedullin 2/intermedin.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=43 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=44 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=45 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=46 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1440 ,  http://www.uniprot.org/uniprot/P30988 \n – – – Subunits – \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=51  (Accessory protein),  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=43 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=43 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=52  (Accessory protein) \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=43 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=53  (Accessory protein) Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P01258 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681 ,  http://www.uniprot.org/uniprot/P06881 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) ≥ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685 ,  http://www.uniprot.org/uniprot/P01258 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) Poorly defined \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ), http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685 ,  http://www.uniprot.org/uniprot/P01258 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P01258 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7588285?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11033437?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565884?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11023820?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10342886?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14722252?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565884?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11023820?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26125036?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ] Sub/family‐selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7482  [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7482  [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7482  [ http://www.ncbi.nlm.nih.gov/pubmed/24169554?dopt=AbstractPlus ] Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=690 ) (p K \n d  9) [ http://www.ncbi.nlm.nih.gov/pubmed/10856900?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=689  (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=689  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=690 ) (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=702  (p K \n d  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/26125036?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=690 ) (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=689  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3776 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3777 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3766 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3770 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3770 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3770 ) (Agonist) \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=47 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=48 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=49 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=50 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16709 ,  http://www.uniprot.org/uniprot/Q16602 \n – – – Subunits – \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=47 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=51  (Accessory protein) \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=47 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=52  (Accessory protein) \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=47 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=53  (Accessory protein) Potency order of endogenous ligands – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:28898 ,  http://www.uniprot.org/uniprot/Q7Z4H4 ) ≥ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=687  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5329 ,  http://www.uniprot.org/uniprot/P10997 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6973 ) Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1438 ,  http://www.uniprot.org/uniprot/P10092 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11693189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9620797?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P06881 )  http://www.uniprot.org/uniprot/P06881 ,  http://www.ncbi.nlm.nih.gov/pubmed/11693189?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11693189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9620797?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:259 ,  http://www.uniprot.org/uniprot/P35318 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11693189?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10347248?dopt=AbstractPlus ] Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=702  (p K \n i  10.7–11) [ http://www.ncbi.nlm.nih.gov/pubmed/10711339?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16959943?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12970090?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24405707?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11847213?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=703  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/18039958?dopt=AbstractPlus ] – – Selective antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=706 ) (p K \n i  7–7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12970090?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=706 ) Labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3766 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6567 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3768 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3768 ) (Agonist)\nIt is important to note that a complication with the interpretation of pharmacological studies with AMY receptors in transfected cells is that most of this work has likely used a mixed population of receptors, encompassing RAMP‐coupled CTR as well as CTR alone. This means that although in binding assays human  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=685  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1437 ,  http://www.uniprot.org/uniprot/P01258 ) has low affinity for 125I‐AMY binding sites, cells transfected with CTR and RAMPs can display potent CT functional responses. Transfection of human CTR with any RAMP can generate receptors with a high affinity for both salmon CT and AMY and varying affinity for different antagonists [ http://www.ncbi.nlm.nih.gov/pubmed/10385705?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16959943?dopt=AbstractPlus ]. The major human CTR splice variant (hCT ( a), which does not contain an insert) with RAMP1 ( i.e.  the AMY 1( a) receptor) has a high affinity for CGRP [ http://www.ncbi.nlm.nih.gov/pubmed/26125036?dopt=AbstractPlus ], unlike hCT ( a)‐RAMP3 ( i.e . AMY 3( a) receptor) [ http://www.ncbi.nlm.nih.gov/pubmed/10385705?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15692146?dopt=AbstractPlus ]. However, the AMY receptor phenotype is RAMP‐type, splice variant and cell‐line‐dependent [ http://www.ncbi.nlm.nih.gov/pubmed/18599553?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22946511?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10871296?dopt=AbstractPlus ]. Emerging data suggests that AMY 1  could be a second CGRP receptor [ http://www.ncbi.nlm.nih.gov/pubmed/29797087?dopt=AbstractPlus ].\nThe ligands described have limited selectivity. Adrenomedullin has appreciable affinity for CGRP receptors. CGRP can show significant cross‐reactivity at AMY receptors and AM 2  receptors. Adrenomedullin 2/intermedin also has high affinity for the AM 2  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/21658025?dopt=AbstractPlus ]. CGRP‐(8‐37) acts as an antagonist of CGRP ( p Ki 8) and inhibits some AM and AMY responses ( p Ki 6‐7). It is weak at CT receptors. HumanAM‐(22‐52)has some selectivity towardsAM receptors, but with modest potency ( p Ki 7), limiting its use [ http://www.ncbi.nlm.nih.gov/pubmed/12970090?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=702  shows the greatest selectivity between receptors but still has significant affinity for AMY 1  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/26125036?dopt=AbstractPlus ].\nGs is a prominent route for effector coupling for CLR and CTR but other pathways ( e.g.  Ca 2+ , ERK, Akt), and G proteins can be activated [ http://www.ncbi.nlm.nih.gov/pubmed/20633935?dopt=AbstractPlus ]. There is evidence that CGRP‐RCP (a 148 amino‐acid hydrophilic protein,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:746  ( http://www.uniprot.org/uniprot/P04424 ) is important for the coupling of CLR to adenylyl cyclase [ http://www.ncbi.nlm.nih.gov/pubmed/10903324?dopt=AbstractPlus ].\n[125I]‐Salmon CT is the most common radioligand for CT receptors but it has high affinity for AMY receptors and is also poorly reversible.\nHay DL  et al . (2018) Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25.  Br. J. Pharmacol. \n 175 : 3‐17 [ https://www.ncbi.nlm.nih.gov/pubmed/29059473?dopt=AbstractPlus ]\nRussell FA  et al . (2014) Calcitonin gene‐related peptide: physiology and pathophysiology.  Physiol. Rev. \n 94 : 1099‐142 [ https://www.ncbi.nlm.nih.gov/pubmed/25287861?dopt=AbstractPlus ]\nHay DL  et al . (2016) Receptor Activity‐Modifying Proteins (RAMPs): New Insights and Roles.  Annu. Rev. Pharmacol. Toxicol. \n 56 : 469‐87 [ https://www.ncbi.nlm.nih.gov/pubmed/26514202?dopt=AbstractPlus ]\nRusso AF. (2015) Calcitonin gene‐related peptide (CGRP): a new target for migraine.  Annu. Rev. Pharmacol. Toxicol. \n 55 : 533‐52 [ https://www.ncbi.nlm.nih.gov/pubmed/25340934?dopt=AbstractPlus ]\nKato J  et al . (2015) Bench‐to‐bedside pharmacology of adrenomedullin.  Eur. J. Pharmacol. \n 764 : 140‐8 [ https://www.ncbi.nlm.nih.gov/pubmed/26144371?dopt=AbstractPlus ]\n\nThe calcium‐sensing receptor (CaS,  provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L‐amino acids (particularly L‐Trp and L‐Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [ http://www.ncbi.nlm.nih.gov/pubmed/24111791?dopt=AbstractPlus ]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [ http://www.ncbi.nlm.nih.gov/pubmed/8255296?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9357776?dopt=AbstractPlus ], L‐amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [ http://www.ncbi.nlm.nih.gov/pubmed/10781086?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10781086?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7493018?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15201280?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9677383?dopt=AbstractPlus ]. Indeed, L‐amino acids have been identified as \"co‐agonists\", with both concomitant calcium and L‐amino acid binding required for full receptor activation [ http://www.ncbi.nlm.nih.gov/pubmed/27434672?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27746744?dopt=AbstractPlus ]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [ http://www.ncbi.nlm.nih.gov/pubmed/25556167?dopt=AbstractPlus ] or decreased extracellular ionic strength [ http://www.ncbi.nlm.nih.gov/pubmed/9677383?dopt=AbstractPlus ]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=54 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1514 ,  http://www.uniprot.org/uniprot/P41180 \n Amino‐acid rank order of potency \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3313 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=717 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3310  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=720  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=726 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3314 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3309  (not L‐lysine, L‐arginine, L‐leucine and L‐isoleucine) [ http://www.ncbi.nlm.nih.gov/pubmed/10781086?dopt=AbstractPlus ] Cation rank order of potency \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2426  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=707  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=708  [ http://www.ncbi.nlm.nih.gov/pubmed/8255296?dopt=AbstractPlus ] Glutamyl peptide rank order of potency S‐methylglutathione ≈ γGlu‐Val‐Gly > glutathione >γGlu‐Cys [ http://www.ncbi.nlm.nih.gov/pubmed/21187282?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19892707?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16455645?dopt=AbstractPlus ] Polyamine rank order of potency \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=710  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2390  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2388  [ http://www.ncbi.nlm.nih.gov/pubmed/9357776?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9475  (Negative) (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/20158186?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9474  (Negative) (pIC 50  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/24900301?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9476  (Negative) (pIC 50  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/19786130?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9473  (Negative) (pIC 50  6.5–6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19442519?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=716  (Negative) (p K \n B  6.2–6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/22210744?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27002221?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23372019?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3308  (Positive) (p K \n B  5.9–6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/25220431?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22210744?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27002221?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=718  (Positive) (p K \n B  6.2–6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/25220431?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25220431?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3947  (Positive) (p K \n B  6.3–6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/25220431?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27002221?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=714  (Negative) (pIC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/14506236?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=719  (Positive) (p K \n B  6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/25220431?dopt=AbstractPlus ]\nThe CaS receptor has a number of physiological functions, but it is best known for its central role in parathyroid and renal regulation of extracellular calcium homeostasis [ http://www.ncbi.nlm.nih.gov/pubmed/27647839?dopt=AbstractPlus ]. This is seen most clearly in patients with loss‐of‐function CaS receptor mutations who develop familial hypocalciuric hypercalcaemia (heterozygous mutations) or neonatal severe hyperparathyroidism (heterozygous, compound heterozygous or homozygous mutations) [ http://www.ncbi.nlm.nih.gov/pubmed/27647839?dopt=AbstractPlus ] and in  Casr  null mice [ http://www.ncbi.nlm.nih.gov/pubmed/18765830?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7493018?dopt=AbstractPlus ], which exhibit similar increases in PTH secretion and blood calcium levels. Gain‐of‐function CaS mutations are associated with autosomal dominant hypocalcaemia and Bartter syndrome type V [ http://www.ncbi.nlm.nih.gov/pubmed/27647839?dopt=AbstractPlus ].\nThe CaS receptor primarily couples to G q/11 , G 12 /13 and G i/o  [ http://www.ncbi.nlm.nih.gov/pubmed/22210744?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16247029?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12954603?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22192592?dopt=AbstractPlus ], but in some cell types can couple to Gs [ http://www.ncbi.nlm.nih.gov/pubmed/20032198?dopt=AbstractPlus ]. However, the CaS receptor can form heteromers with Class C GABAB [ http://www.ncbi.nlm.nih.gov/pubmed/17591780?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17615148?dopt=AbstractPlus ] and mGlu1/5 receptors [ http://www.ncbi.nlm.nih.gov/pubmed/11489900?dopt=AbstractPlus ], which may introduce further complexity in its signalling capabilities.\nMultiple other small molecule chemotypes are positive and negative allosteric modulators of the CaS receptor [ http://www.ncbi.nlm.nih.gov/pubmed/21406038?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24050279?dopt=AbstractPlus ]. Further,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8375  is a novel peptide positive allosteric modulator of the receptor [ http://www.ncbi.nlm.nih.gov/pubmed/23674604?dopt=AbstractPlus ]. Agonists and positive allosteric modulators of the CaS receptor are termed Type I and II calcimimetics, respectively, and can suppress parathyroid hormone ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ,  http://www.uniprot.org/uniprot/P01270 )) secretion [ http://www.ncbi.nlm.nih.gov/pubmed/9520489?dopt=AbstractPlus ]. Negative allosteric modulators are called calcilytics and can act to increase  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ) secretion [ http://www.ncbi.nlm.nih.gov/pubmed/11561095?dopt=AbstractPlus ].\nWhere functional pKB values are provided for allosteric modulators, this refers to ligand affinity determined in an assay that measures a functional readout of receptor activity ( i.e.  a receptor signalling assay), as opposed to affinity determined in a radioligand binding assay. The functional pKB may differ depending on the signalling pathway studied. Consult the  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=54&familyId=12&familyType=GPCR#Allosterics  for the assay description, as well as other functional readouts.\nBrown EM. (2013) Role of the calcium‐sensing receptor in extracellular calcium homeostasis.  Best Pract. Res. Clin. Endocrinol. Metab. \n 27 : 333‐43 [ https://www.ncbi.nlm.nih.gov/pubmed/23856263?dopt=AbstractPlus ]\nHannan FM  et al . (2018) The calcium‐sensing receptor in physiology and in calcitropic and noncal citropic diseases.  Nat Rev Endocrinol \n 15 : 33‐51 [ https://www.ncbi.nlm.nih.gov/pubmed/30443043?dopt=AbstractPlus ]\nConigrave AD  et al . (2013) Calcium‐sensing receptor (CaSR): pharmacological properties and signaling pathways.  Best Pract. Res. Clin. Endocrinol. Metab. \n 27 : 315‐31 [ https://www.ncbi.nlm.nih.gov/pubmed/23856262?dopt=AbstractPlus ]\nNemeth EF  et al . (2018) Discovery and Development of Calcimimetic and Calcilytic Compounds.  Prog Med Chem \n 57 : 1‐86 [ https://www.ncbi.nlm.nih.gov/pubmed/29680147?dopt=AbstractPlus ]\n\nCannabinoid receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Cannabinoid Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]) are activated by endogenous ligands that include N‐arachidonoylethanolamine ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2364 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5444 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5444 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5445  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=729 . Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [ http://www.ncbi.nlm.nih.gov/pubmed/17876303?dopt=AbstractPlus ].\nThere are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB 1  and CB 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/23108552?dopt=AbstractPlus ]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9071  (Cesamet®), a synthetic CB 1 /CB 2  receptor agonist, and synthetic  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424  (Marinol®; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4150 , both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=56 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=56 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=57 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=57 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2159 ,  http://www.uniprot.org/uniprot/P21554 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2160 ,  http://www.uniprot.org/uniprot/P34972 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=731  [ http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8819477?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=730 ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=733 ,  http://www.ncbi.nlm.nih.gov/pubmed/8679694?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8679694?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=740  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=731  [ http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9379442?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8819477?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=733 ,  http://www.ncbi.nlm.nih.gov/pubmed/8679694?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8679694?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=730 ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8626625?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8626625?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9379442?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8819477?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=738  [ http://www.ncbi.nlm.nih.gov/pubmed/10336536?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=739 ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=732  [ http://www.ncbi.nlm.nih.gov/pubmed/11181068?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2506  [ http://www.ncbi.nlm.nih.gov/pubmed/8893848?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=747  [ http://www.ncbi.nlm.nih.gov/pubmed/10658595?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11060760?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=748  [ 0663 ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3316  [ http://www.ncbi.nlm.nih.gov/pubmed/16894349?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=749  [ 0663 ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=746  [ http://www.ncbi.nlm.nih.gov/pubmed/10588688?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=743  (p K \n i  7.9–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9435190?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7565624?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8070571?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12663689?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8819477?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10029  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/25535367?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3317  (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10052983?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=741  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/11741201?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=742  (p K \n i  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9435190?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=751  (p K \n i  8.3–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9454810?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=750  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/10188977?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9237  (Negative) (pEC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/26529344?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9239  (Positive) (pEC 50  6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/26052038?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10272  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/28103441?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4150  (Negative) [ http://www.ncbi.nlm.nih.gov/pubmed/26218440?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9188  (Positive) (p K i ∼7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/28842619?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10273  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/29990428?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=745  (Antagonist) (p K \n d  8.9–10) [ http://www.ncbi.nlm.nih.gov/pubmed/9316881?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8981483?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8978752?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8733746?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8614277?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8987831?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9536023?dopt=AbstractPlus ] – Rat –\nBoth CB 1  and CB 2  receptors may be labelled with [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=734  (0.5 nM;[ http://www.ncbi.nlm.nih.gov/pubmed/8819477?dopt=AbstractPlus ]) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=736  (2‐2.4 nM; [ http://www.ncbi.nlm.nih.gov/pubmed/7651369?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8622639?dopt=AbstractPlus ]).  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2364  is also an agonist at vanilloid receptors ( http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=78%23show_object_507 )and  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=86  [ http://www.ncbi.nlm.nih.gov/pubmed/17704824?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10440374?dopt=AbstractPlus ]. There is evidence for an allosteric site on the CB 1  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/16113085?dopt=AbstractPlus ]. All of the compounds listed as antagonists behave as inverse agonists in some bioassay systems [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]. For some cannabinoid receptor ligands, additional pharmacological targets that include GPR55 and GPR119 have been identified [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]. Moreover,  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=114  although showing little structural similarity to CB 1  and CB 2  receptors, respond to endogenous agents that are structurally similar to the endogenous cannabinoid ligands [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ].\nHowlett AC  et al . (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors.  Pharmacol. Rev. \n 54 : 161‐202 [ https://www.ncbi.nlm.nih.gov/pubmed/12037135?dopt=AbstractPlus ]\nPertwee RG  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB_1 and CB_2.  Pharmacol. Rev. \n 62 : 588‐631 [ https://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]\nPertwee RG. (2010) Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists.  Curr. Med. Chem. \n 17 : 1360‐81 [ https://www.ncbi.nlm.nih.gov/pubmed/20166927?dopt=AbstractPlus ]\n\nNomenclature for the chemerin receptors is presented as  recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/29279348?dopt=AbstractPlus ]). The chemoattractant protein and adipokine,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2945  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9868 ,  http://www.uniprot.org/uniprot/Q99969 ), has been shown to be the endogenous ligand for both chemerin family receptors. Chemerin 1  was the founding family member, and when  GPR1  was de‐orphanised it was re‐named Chermerin 2  [ http://www.ncbi.nlm.nih.gov/pubmed/29279348?dopt=AbstractPlus ]. Chemerin 1  is also activated by the lipid‐derived, antiinflammatory ligand  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3333  (RvE1), which is formed  via  the sequential metabolism of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3362  by aspirin‐modified cyclooxygenase and lipoxygenase [ http://www.ncbi.nlm.nih.gov/pubmed/15753205?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17339491?dopt=AbstractPlus ]. In addition, two GPCRs for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  (RvD1) have been identified: FPR2/ALX, the lipoxin A4 receptor, and GPR32, an orphan receptor [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=79 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=82 \n Common abbreviation Chemerin 1 \n Chemerin 2 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2121 ,  http://www.uniprot.org/uniprot/Q99788 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4463 ,  http://www.uniprot.org/uniprot/P46091 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3333  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3422  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3400  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3362  [ http://www.ncbi.nlm.nih.gov/pubmed/15753205?dopt=AbstractPlus ] – Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2945  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9868 ,  http://www.uniprot.org/uniprot/Q99969 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18165312?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3333 \n – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2901  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15753205?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17339491?dopt=AbstractPlus ] – Comments – Reported to act as a co‐receptor for HIV [ http://www.ncbi.nlm.nih.gov/pubmed/10233994?dopt=AbstractPlus ]. See review [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] for discussion of pairing with chemerin.\nCCX832 (structure not disclosed) is a selective antagonist, p K i=9.2 [ http://www.ncbi.nlm.nih.gov/pubmed/27742615?dopt=AbstractPlus ].\nKennedy AJ  et al . (2018) International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function.  Pharmacol. Rev. \n 70 : 174‐196 [ https://www.ncbi.nlm.nih.gov/pubmed/29279348?dopt=AbstractPlus ]\nShin WJ  et al . (2018) Mechanisms and Functions of Chemerin in Cancer: Potential Roles in Therapeutic Intervention.  Front Immunol \n 9 : 2772 [ https://www.ncbi.nlm.nih.gov/pubmed/30555465?dopt=AbstractPlus ]\n\nChemokine receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Chemokine Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12037138?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10699158?dopt=AbstractPlus ]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non‐hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein‐coupled chemokine receptors, which mediate leukocyte trafficking, and \"Atypical chemokine receptors\", which may signal through non‐G protein‐coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [ http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus ].\nChemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β‐chemokines;  n = 28), CXC (also known as α‐chemokines;  n = 17) and CX3C ( n = 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines ( n = 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high‐affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein‐coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [ http://www.ncbi.nlm.nih.gov/pubmed/25958743?dopt=AbstractPlus ]. There can be substantial cross‐species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non‐chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co‐receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include bothstandard chemokine receptor names [ http://www.ncbi.nlm.nih.gov/pubmed/10714678?dopt=AbstractPlus ] and aliases.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=58 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=59 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=60 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1602 ,  http://www.uniprot.org/uniprot/P32246 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1603 ,  http://www.uniprot.org/uniprot/P41597 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1604 ,  http://www.uniprot.org/uniprot/P51677 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=756  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10627 ,  http://www.uniprot.org/uniprot/P10147 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12381680?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8530354?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9624164?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11170631?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=755  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10622 ,  http://www.uniprot.org/uniprot/P55773 )  http://www.uniprot.org/uniprot/P55773 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8530354?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8530354?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 )  http://www.uniprot.org/uniprot/P80098 ,  http://www.ncbi.nlm.nih.gov/pubmed/11994538?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=754  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10613 ,  http://www.uniprot.org/uniprot/Q16663 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9346309?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=753  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10612 ,  http://www.uniprot.org/uniprot/Q16627 )  http://www.uniprot.org/uniprot/Q16627 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=770  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10611 ,  http://www.uniprot.org/uniprot/Q99616 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=772  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10635 ,  http://www.uniprot.org/uniprot/P80075 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=771  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10618 ,  http://www.uniprot.org/uniprot/P13500 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9346309?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12554737?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10770925?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15207250?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9276730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=770  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10611 ,  http://www.uniprot.org/uniprot/Q99616 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12554737?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12554737?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 )  http://www.uniprot.org/uniprot/P80098 ,  http://www.ncbi.nlm.nih.gov/pubmed/9346309?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9276730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ) (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12554737?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15207250?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1272  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10614 ,  http://www.uniprot.org/uniprot/O15467 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=770  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10611 ,  http://www.uniprot.org/uniprot/Q99616 ) [ http://www.ncbi.nlm.nih.gov/pubmed/16339911?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9276730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=775  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10623 ,  http://www.uniprot.org/uniprot/O00175 )  http://www.uniprot.org/uniprot/O00175 ,  http://www.ncbi.nlm.nih.gov/pubmed/15207250?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8642344?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8642344?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12761559?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10488147?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10488147?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10854442?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9276730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=776  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10625 ,  http://www.uniprot.org/uniprot/Q9Y258 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10488147?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10488147?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16339911?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=754  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10613 ,  http://www.uniprot.org/uniprot/Q16663 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9346309?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3649  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17700 ,  http://www.uniprot.org/uniprot/Q9NRJ3 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=772  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10635 ,  http://www.uniprot.org/uniprot/P80075 ) Agonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=787  {Mouse} [ http://www.ncbi.nlm.nih.gov/pubmed/8642344?dopt=AbstractPlus ] Endogenous antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=757  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10630 ,  http://www.uniprot.org/uniprot/P13236 ) (p K \n i  7.1–7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12381680?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8530354?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=776  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10625 ,  http://www.uniprot.org/uniprot/Q9Y258 ) (pIC 50  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/15207250?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=835  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10637 ,  http://www.uniprot.org/uniprot/P02778 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=836  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10638 ,  http://www.uniprot.org/uniprot/O14625 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=837  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7098 ,  http://www.uniprot.org/uniprot/Q07325 ) Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=767  (p K \n i  8.2–9) [ http://www.ncbi.nlm.nih.gov/pubmed/10748002?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3696  (pIC 50  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12614873?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3536  (pIC 50  8) [ http://www.ncbi.nlm.nih.gov/pubmed/10854442?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3497  (p K \n d  8) [ http://www.ncbi.nlm.nih.gov/pubmed/12909630?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3502  (p K \n i  7.6) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=796 ) (Inverse agonist) (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/12450563?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3530  (p K i 8.4),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3492  (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/12067561?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=765 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7545673?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=763 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7545673?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9115216?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9336350?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=764 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9336350?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=762 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=765 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=794 ) (Antagonist) (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/12450563?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=764 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=765 ) (Agonist) \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=61 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=62 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=63 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=64 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=65 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=66 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=67 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1605 ,  http://www.uniprot.org/uniprot/P51679 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1606 ,  http://www.uniprot.org/uniprot/P51681 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1607 ,  http://www.uniprot.org/uniprot/P51684 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1608 ,  http://www.uniprot.org/uniprot/P32248 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1609 ,  http://www.uniprot.org/uniprot/P51685 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1610 ,  http://www.uniprot.org/uniprot/P51686 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4474 ,  http://www.uniprot.org/uniprot/P46092 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=798  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10621 ,  http://www.uniprot.org/uniprot/O00626 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9430724?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=797  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10615 ,  http://www.uniprot.org/uniprot/Q92583 )  http://www.uniprot.org/uniprot/Q92583 ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10318947?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9790730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=757  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10630 ,  http://www.uniprot.org/uniprot/P13236  [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9790730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=772  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10635 ,  http://www.uniprot.org/uniprot/P80075 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9790730?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=756  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10627 ,  http://www.uniprot.org/uniprot/P10147 )[ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11170631?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10477718?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=771  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10618 ,  http://www.uniprot.org/uniprot/P13500  [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=753  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10612 ,  http://www.uniprot.org/uniprot/Q16627  [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1272  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10614 ,  http://www.uniprot.org/uniprot/O15467 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=808  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10619 ,  http://www.uniprot.org/uniprot/P78556 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12081481?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9169459?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9294137?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3648  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2767 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30193 ,  http://www.uniprot.org/uniprot/O15263 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10521347?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=811  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10620 ,  http://www.uniprot.org/uniprot/O00585 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9507024?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=810  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10617 ,  http://www.uniprot.org/uniprot/Q99731 ) [ http://www.ncbi.nlm.nih.gov/pubmed/16904643?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9153236?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9153236?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=812  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10609 ,  http://www.uniprot.org/uniprot/P22362 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10419462?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16221874?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11154210?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4415  {Mouse} \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=817  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10624 ,  http://www.uniprot.org/uniprot/O15444 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3646  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10626 ,  http://www.uniprot.org/uniprot/Q9Y4X3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10725697?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3649  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17700 ,  http://www.uniprot.org/uniprot/Q9NRJ3 ) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4359 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3910 \n – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=815  [ http://www.ncbi.nlm.nih.gov/pubmed/10419462?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11154210?dopt=AbstractPlus ] – – Endogenous antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 ) (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ] – – – – – Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=807  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16304152?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=804  (p K \n i  7.8–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/16476734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11585437?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11585437?dopt=AbstractPlus ] – – – – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9478  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/19081254?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3500  (pIC 50  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11454872?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=805  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/16476734?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=806  (pIC 50  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=783  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/16476734?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3651  [ http://www.ncbi.nlm.nih.gov/pubmed/12604693?dopt=AbstractPlus ] – Rat – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=816  (pIC 50  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10419462?dopt=AbstractPlus ] – – Selective allosteric modulators – – – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9046  (Antagonist) (pIC 50  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/20660125?dopt=AbstractPlus ] – Antibodies \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6477  (Inhibition) [ http://www.ncbi.nlm.nih.gov/pubmed/21154168?dopt=AbstractPlus , 1962] – – – – – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3652 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3653 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=799 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16298345?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=763 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=764 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=766 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3654 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9294138?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3655 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3656 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10201891?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=814 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11154210?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9211859?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3657 ) (Agonist) – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=68 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=69 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=70 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=71 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=72 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=73 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=74 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6026 ,  http://www.uniprot.org/uniprot/P25024 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6027 ,  http://www.uniprot.org/uniprot/P25025 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4540 ,  http://www.uniprot.org/uniprot/P49682 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2561 ,  http://www.uniprot.org/uniprot/P61073 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1060 ,  http://www.uniprot.org/uniprot/P32302 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16647 ,  http://www.uniprot.org/uniprot/O00574 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2558 ,  http://www.uniprot.org/uniprot/P49238 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=821  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6025 ,  http://www.uniprot.org/uniprot/P10145 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15282370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10188995?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1379593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15946947?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8940121?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=820  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10643 ,  http://www.uniprot.org/uniprot/P80162 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9692902?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=819  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4602 ,  http://www.uniprot.org/uniprot/P09341 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10188995?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1379593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8940121?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=821  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6025 ,  http://www.uniprot.org/uniprot/P10145 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15282370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15282370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1379593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15946947?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8940121?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=830  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9240 ,  http://www.uniprot.org/uniprot/P02775 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8702798?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=828  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4604 ,  http://www.uniprot.org/uniprot/P19876 )  http://www.uniprot.org/uniprot/P19876 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=827  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4603 ,  http://www.uniprot.org/uniprot/P19875 )  http://www.uniprot.org/uniprot/P19875 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=829  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10642 ,  http://www.uniprot.org/uniprot/P42830 )  http://www.uniprot.org/uniprot/P42830 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=820  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10643 ,  http://www.uniprot.org/uniprot/P80162 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9692902?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=836  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10638 ,  http://www.uniprot.org/uniprot/O14625 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15761110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=835  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10637 ,  http://www.uniprot.org/uniprot/P02778 )  http://www.uniprot.org/uniprot/P02778 ,  http://www.ncbi.nlm.nih.gov/pubmed/9660793?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=837  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7098 ,  http://www.uniprot.org/uniprot/Q07325 )  http://www.uniprot.org/uniprot/Q07325 ,  http://www.ncbi.nlm.nih.gov/pubmed/15761110?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4358  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10672 ,  http://www.uniprot.org/uniprot/P48061 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9551924?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9712844?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=845  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10672 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10672 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9551924?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3645  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10639 ,  http://www.uniprot.org/uniprot/O43927 ) [ http://www.ncbi.nlm.nih.gov/pubmed/22913878?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=855  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16642 ,  http://www.uniprot.org/uniprot/Q9H2A7 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11290797?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=856  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10647 ,  http://www.uniprot.org/uniprot/P78423 ) [ http://www.ncbi.nlm.nih.gov/pubmed/14607932?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8496  [ http://www.ncbi.nlm.nih.gov/pubmed/20044480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8495  [ http://www.ncbi.nlm.nih.gov/pubmed/22262769?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8496  [ http://www.ncbi.nlm.nih.gov/pubmed/20044480?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8495  [ http://www.ncbi.nlm.nih.gov/pubmed/22262769?dopt=AbstractPlus ] – – – – – Selective agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=607  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11923301?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3919 \n – – – Endogenous antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ) (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9660793?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 ) (p K \n i  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/9660793?dopt=AbstractPlus ] – – – – Antagonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=844  (p K \n i  7) [ http://www.ncbi.nlm.nih.gov/pubmed/11923301?dopt=AbstractPlus ] – – – Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8497  (pIC 50  10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17181143?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8500  (pIC 50  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/26092545?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=833  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9553055?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8499  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8501  (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/25254640?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=852  (pIC 50  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9918823?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8580  (pIC 50  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/20297846?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=773 \n – – – Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8498  (Negative) (pIC 50  9) [ http://www.ncbi.nlm.nih.gov/pubmed/15282370?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8498  (Negative) (pIC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/15282370?dopt=AbstractPlus ] – – – – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=822 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10188995?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12626541?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=822 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10188995?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12626541?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3677 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3659 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3658 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3660 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3661 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=849  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=849 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11104827?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9551924?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8631 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/24190631?dopt=AbstractPlus ] – Mouse [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3662 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3664 ) (Agonist) \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=75 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=316 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=314 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=80 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=315 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=78 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1625 ,  http://www.uniprot.org/uniprot/P46094 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4035 ,  http://www.uniprot.org/uniprot/Q16570 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1565 ,  http://www.uniprot.org/uniprot/O00590 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23692 ,  http://www.uniprot.org/uniprot/P25106 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1611 ,  http://www.uniprot.org/uniprot/Q9NPB9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1612 ,  http://www.uniprot.org/uniprot/O00421 \n Endogenous ligands – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=829  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10642 ,  http://www.uniprot.org/uniprot/P42830 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=820  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10643 ,  http://www.uniprot.org/uniprot/P80162 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=821  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6025 ,  http://www.uniprot.org/uniprot/P10145 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=836  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10638 ,  http://www.uniprot.org/uniprot/O14625 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=771  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10618 ,  http://www.uniprot.org/uniprot/P13500 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=753  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10612 ,  http://www.uniprot.org/uniprot/Q16627 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=797  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10615 ,  http://www.uniprot.org/uniprot/Q92583 ) – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3422 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=810  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10617 ,  http://www.uniprot.org/uniprot/Q99731 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18165312?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3647  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10645 ,  http://www.uniprot.org/uniprot/P47992 ) [ http://www.ncbi.nlm.nih.gov/pubmed/25497737?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4370  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10646 ,  http://www.uniprot.org/uniprot/Q9UBD3 )  http://www.uniprot.org/uniprot/Q9UBD3 ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=771  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10618 ,  http://www.uniprot.org/uniprot/P13500 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=756  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10627 ,  http://www.uniprot.org/uniprot/P10147 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=757  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10630 ,  http://www.uniprot.org/uniprot/P13236 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=758  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10632 ,  http://www.uniprot.org/uniprot/P13501 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=759  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10634 ,  http://www.uniprot.org/uniprot/P80098 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=772  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10635 ,  http://www.uniprot.org/uniprot/P80075 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=769  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10610 ,  http://www.uniprot.org/uniprot/P51671 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=770  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10611 ,  http://www.uniprot.org/uniprot/Q99616 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=753  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10612 ,  http://www.uniprot.org/uniprot/Q16627 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=797  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10615 ,  http://www.uniprot.org/uniprot/Q92583 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=798  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10621 ,  http://www.uniprot.org/uniprot/O00626 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4358  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10672 ,  http://www.uniprot.org/uniprot/P48061 ) [ http://www.ncbi.nlm.nih.gov/pubmed/20956518?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=836  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10638 ,  http://www.uniprot.org/uniprot/O14625 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=810  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10617 ,  http://www.uniprot.org/uniprot/Q99731 ) [ http://www.ncbi.nlm.nih.gov/pubmed/23341447?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=817  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10624 ,  http://www.uniprot.org/uniprot/O15444 )  http://www.uniprot.org/uniprot/O15444 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=811  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10620 ,  http://www.uniprot.org/uniprot/O00585 )  http://www.uniprot.org/uniprot/O00585 ] – Comments XCL1 cannot be iodinated, but a secreted alkaline phophatase (SEAP)‐XCL1 fusion peptide can be used as a probe at XCR1. ACKR1 is used by  Plasmodium vivax  and  Plasmodium knowlsei  for entering erythrocytes. – Several lines of evidence have suggested that CGRP and adrenomedullin could be ligands for ACKR3; however, classical direct binding to the receptor has not yet been convincingly demonstrated [ http://www.ncbi.nlm.nih.gov/pubmed/29530506?dopt=AbstractPlus ]. – –\nSpecific chemokine receptors facilitate cell entry by microbes, such as ACKR1 for  Plasmodium vivax , and CCR5 and CXCR4 for HIV‐1. Virally encoded chemokine receptors are known ( e.g.  US28, a homologue of CCR1 from human cytomegalovirus and ORF74, which encodes a homolog of CXCR2 in  Herpesvirus saimiri  and gamma‐Herpesvirus‐68), but their role in viral life cycles is not established. Viruses can exploit or subvert the chemokine system by producing chemokine antagonists and scavengers. Three chemokine receptor antagonists have now been approved by the FDA: 1) the CCR5 antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=806  (Pfizer) for treatment of HIV/AIDS in patients with CCR5‐using strains; and 2) the CXCR4 antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=844  (Sanofi) for hematopoietic stem cell mobilization with  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4934  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2438 ,  http://www.uniprot.org/uniprot/P09919 ) in patients undergoing transplantation in the context of chemotherapy for Hodgkins’ Disease and multiple myeloma; and 3) the CCR4 blocking antibody Poteligeo (mogamulizumab‐kpkc, Kyowa Kirin, Inc.) for mycosis fungoides or Sezary syndrome.\nBachelerie F  et al . (2015) An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15.  Br. J. Pharmacol. \n 172 : 3945‐9 [ https://www.ncbi.nlm.nih.gov/pubmed/25958743?dopt=AbstractPlus ]\nMurphy PM  et al . (2000) International Union of Pharmacology. XXII. Nomenclature for chemokine receptors.  Pharmacol. Rev. \n 52 : 145‐176 [ https://www.ncbi.nlm.nih.gov/pubmed/10699158?dopt=AbstractPlus ]\nKoelink PJ  et al . (2012) Targeting chemokine receptors in chronic inflammatory diseases: an extensive review.  Pharmacol. Ther. \n 133 : 1‐18 [ https://www.ncbi.nlm.nih.gov/pubmed/21839114?dopt=AbstractPlus ]\nScholten DJ  et al . (2012) Pharmacological modulation of chemokine receptor function.  Br. J. Pharmacol. \n 165 : 1617‐43 [ https://www.ncbi.nlm.nih.gov/pubmed/21699506?dopt=AbstractPlus ]\nMurphy PM. (2002) International Union of Pharmacology. XXX. Update on chemokine receptor nomenclature.  Pharmacol. Rev. \n 54 : 227‐9 [ https://www.ncbi.nlm.nih.gov/pubmed/12037138?dopt=AbstractPlus ]\n\nCholecystokinin receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on CCK receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/10581329?dopt=AbstractPlus ) are activated by the endogenous peptides cholecystokinin‐8 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=864  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ,  http://www.uniprot.org/uniprot/P06307 )),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=860 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3552 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ) and gastrin ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3559  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ,  http://www.uniprot.org/uniprot/P01350 )). There are only two distinct subtypes of CCK receptors, CCK 1  and CCK 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/1373504?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1313582?dopt=AbstractPlus ], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK 1  receptor requiring the carboxyl‐terminal heptapeptide‐amide that includes a sulfated tyrosine for high affinity and potency, while the CCK 2  receptor requires only the carboxyl‐terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=76 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=77 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1570 ,  http://www.uniprot.org/uniprot/P32238 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1571 ,  http://www.uniprot.org/uniprot/P32239 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=864  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ,  http://www.uniprot.org/uniprot/P06307 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3552 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10221 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=860 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 )  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3559  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ,  http://www.uniprot.org/uniprot/P01350 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3725  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=861 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=864  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ,  http://www.uniprot.org/uniprot/P06307 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10221 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=860 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3552 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3559  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ,  http://www.uniprot.org/uniprot/P01350 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3725 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=861 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ) Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=860  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ,  http://www.uniprot.org/uniprot/P06307 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10221 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3552 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=864 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3725  [ http://www.ncbi.nlm.nih.gov/pubmed/7681836?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3559  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ,  http://www.uniprot.org/uniprot/P01350 ) [ http://www.ncbi.nlm.nih.gov/pubmed/1975695?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=861  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1569 ,  http://www.uniprot.org/uniprot/P06307 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8349705?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3558 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8408 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8409 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8410 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8411 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3562 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3566 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4164 ) Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=858  [ http://www.ncbi.nlm.nih.gov/pubmed/1636779?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3888  [ http://www.ncbi.nlm.nih.gov/pubmed/7654246?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=865  [ http://www.ncbi.nlm.nih.gov/pubmed/9276016?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=900  [ http://www.ncbi.nlm.nih.gov/pubmed/14698161?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3948  [ http://www.ncbi.nlm.nih.gov/pubmed/8720482?dopt=AbstractPlus ] – Rat Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=890  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10988332?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=878  (pIC 50  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/1975695?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=884  (pIC 50  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/8813597?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=904  (pIC 50  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/8605955?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=891  (pIC 50  6.7–8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/1975695?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2437574?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=887  (pIC 50  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/22607579?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9042983?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3503  (pIC 50  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/11020274?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=881  (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/11738246?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=888  (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/11738246?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6665  (pIC 50  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/21493750?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=879  (pIC 50  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7681836?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3523  (pIC 50  8) [ http://www.ncbi.nlm.nih.gov/pubmed/10385255?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3509  (pIC 50  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/21228869?dopt=AbstractPlus ] – Rat Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3476  (Antagonist) (p K \n d  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/3018478?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6666  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/3410633?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3478  (Antagonist) (p K \n i  9.7–10) [ http://www.ncbi.nlm.nih.gov/pubmed/8474432?dopt=AbstractPlus ] – Guinea pig, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3472  (Antagonist) (p K \n d  9.6) [ 0905 ] – Guinea pig, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6666  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/3410633?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3781  (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3821  (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3477  (Antagonist) (p K \n d  8.2–8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11738246?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6667  (Antagonist) (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/19271701?dopt=AbstractPlus ]\nWhile a cancer‐specific CCK receptor has been postulated to exist, which also might be responsive to incompletely processed forms of CCK (Gly‐extended forms), this has never been isolated. An alternatively spliced form of the CCK 2  receptor in which intron 4 is retained, adding 69 amino acids to the intracellular loop 3 (ICL3) region, has been described to be present particularly in certain neoplasms where mRNA mis‐splicing has been commonly observed [ http://www.ncbi.nlm.nih.gov/pubmed/12429993?dopt=AbstractPlus ], but it is not clear that this receptor splice form plays a special role in carcinogenesis. Another alternative splicing event for the CCK 2  receptor was reported [ http://www.ncbi.nlm.nih.gov/pubmed/8415658?dopt=AbstractPlus ], with alternative donor sites in exon 4 resulting in long (452 amino acids) and short (447 amino acids) forms of the receptor differing by five residues in ICL3, however, no clear functional differences have been observed.\nBallaz S. (2017) The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning.  Rev Neurosci \n 28 : 573‐585 [ https://www.ncbi.nlm.nih.gov/pubmed/28343167?dopt=AbstractPlus ]\nDockray GJ. (2009) Cholecystokinin and gut‐brain signalling.  Regul. Pept. \n 155 : 6‐10 [ https://www.ncbi.nlm.nih.gov/pubmed/19345244?dopt=AbstractPlus ]\nCawston EE  et al . (2010) Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor.  Br. J. Pharmacol. \n 159 : 1009‐21 [ https://www.ncbi.nlm.nih.gov/pubmed/19922535?dopt=AbstractPlus ]\nDufresne M  et al . (2006) Cholecystokinin and gastrin receptors.  Physiol. Rev. \n 86 : 805‐47 [ https://www.ncbi.nlm.nih.gov/pubmed/16816139?dopt=AbstractPlus ]\n\nReceptors of the Class Frizzled (FZD,  nomenclature as agreed by the  NC‐IUPHAR  subcommittee on the Class Frizzled GPCRs  [ http://www.ncbi.nlm.nih.gov/pubmed/21079039?dopt=AbstractPlus ]), are GPCRs originally identified in  Drosophila  [ http://www.ncbi.nlm.nih.gov/pubmed/1334084?dopt=AbstractPlus ], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it mediates effects in the Hedgehog signaling pathway [ http://www.ncbi.nlm.nih.gov/pubmed/21079039?dopt=AbstractPlus ]. FZDs are activated by WNTs, which are cysteine‐rich lipoglycoproteins withfundamentalfunctions inontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5371  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2514 ,  http://www.uniprot.org/uniprot/P35222 ) or being β‐catenin‐independent (often referred to as canonical  vs.  non‐canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6697  ( http://www.uniprot.org/uniprot/O75197 ) and  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6698  ( http://www.uniprot.org/uniprot/O75581 ), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β‐catenin and subsequently its translocation to the nucleus. β‐Catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. βCatenin‐independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [ http://www.ncbi.nlm.nih.gov/pubmed/24032637?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28790300?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30049420?dopt=AbstractPlus ], the elevation of intracellular calcium [ http://www.ncbi.nlm.nih.gov/pubmed/9389482?dopt=AbstractPlus ], activation of cGMP‐specific PDE6 [ http://www.ncbi.nlm.nih.gov/pubmed/12471263?dopt=AbstractPlus ] and elevation of cAMP as well as RAC‐1, JNK, Rho and Rho kinase signalling [ http://www.ncbi.nlm.nih.gov/pubmed/19651774?dopt=AbstractPlus ]. Novel resonance energy transfer‐based tools have allowed the study of the GPCR‐like nature of FZDs in greater detail. Upon ligand stimulation, FZDs undergo conformational changes and signal  via  heterotrimeric G proteins [ http://www.ncbi.nlm.nih.gov/pubmed/30514810?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30737406?dopt=AbstractPlus ]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling. Importantly, FZDs exist in at least two distinct conformational states that regulate the pathway selection [ http://www.ncbi.nlm.nih.gov/pubmed/30737406?dopt=AbstractPlus ]. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [ http://www.ncbi.nlm.nih.gov/pubmed/12958365?dopt=AbstractPlus ], as well as for β‐catenin‐dependent [ http://www.ncbi.nlm.nih.gov/pubmed/17426148?dopt=AbstractPlus ] and ‐independent [ http://www.ncbi.nlm.nih.gov/pubmed/18953287?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17476309?dopt=AbstractPlus ] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled‐related proteins (sFRP),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5372  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18081 ,  http://www.uniprot.org/uniprot/Q9Y5W5 ) (WIF),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3704  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13771 ,  http://www.uniprot.org/uniprot/Q9BQB4 ) or Dickkopf (DKK)), as well as modulatory (co)‐receptors with  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=304#Type XV RTKs: RYK ,  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=304#Type VIII RTKs: ROR1 ,  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=304#Type VIII RTKs: ROR2  and Kremen, which may also function as independent signalling proteins.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=229 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=230 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=231 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=232 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=233 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4038 ,  http://www.uniprot.org/uniprot/Q9UP38 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4040 ,  http://www.uniprot.org/uniprot/Q14332 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4041 ,  http://www.uniprot.org/uniprot/Q9NPG1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4042 ,  http://www.uniprot.org/uniprot/Q9ULV1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4043 ,  http://www.uniprot.org/uniprot/Q13467 \n Allosteric modulators – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10321  (Negative) (pIC 50  5.5–7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/25751279?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10321  (Positive) (pEC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/29293331?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10322  (Negative) (pIC 50  6.2) [ http://www.ncbi.nlm.nih.gov/pubmed/25751279?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25751279?dopt=AbstractPlus ] – Antibodies \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10197  (Antagonist) (pIC 50  ∼9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/22753465?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10197  (Antagonist) (pIC 50  ∼9) [ http://www.ncbi.nlm.nih.gov/pubmed/22753465?dopt=AbstractPlus ] – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10197  (Antagonist) (pIC 50  ∼9) [ http://www.ncbi.nlm.nih.gov/pubmed/22753465?dopt=AbstractPlus ] Comments – – – – IgG‐2919 and IgG‐2921 are FZD5 antibodies that have exhibited antitumour activities  in vitro  and  in vivo  (inhibiting the growth of RNF43‐mutant pancreatic ductal adenocarcinoma cells/xenograft tumours), by blocking autocrine Wnt‐β‐catenin signalling in these mutant, FZD5‐dependent cells [ http://www.ncbi.nlm.nih.gov/pubmed/27869803?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=234 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=235 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=236 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=237 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=238 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4044 ,  http://www.uniprot.org/uniprot/O60353 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4045 ,  http://www.uniprot.org/uniprot/O75084 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4046 ,  http://www.uniprot.org/uniprot/Q9H461 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4047 ,  http://www.uniprot.org/uniprot/O00144 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4039 ,  http://www.uniprot.org/uniprot/Q9ULW2 \n Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10324  (pIC 50  7) [ http://www.ncbi.nlm.nih.gov/pubmed/29632413?dopt=AbstractPlus ] – – – Antibodies – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10197  (Antagonist) (pIC 50  ∼9) [ http://www.ncbi.nlm.nih.gov/pubmed/22753465?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10197  (Antagonist) (pIC 50  ∼8) [ http://www.ncbi.nlm.nih.gov/pubmed/22753465?dopt=AbstractPlus ] – – Comments – – FZD8‐Fc/OMP‐54F28 is a FZD8 antagonist [ http://www.ncbi.nlm.nih.gov/pubmed/17545618?dopt=AbstractPlus ]. – Radio‐labelled murine monoclonal antibody MAb 92‐13 has been used to demonstrate the therapeutic potential of targeting FZD10‐positive tumours [ http://www.ncbi.nlm.nih.gov/pubmed/18271942?dopt=AbstractPlus ]. \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=239 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11119 ,  http://www.uniprot.org/uniprot/Q99835 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10327 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12391318?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10356  [ http://www.ncbi.nlm.nih.gov/pubmed/16408088?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10332  (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/25636740?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10330  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12391318?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10329  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/10984056?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10328  (pIC 50  ∼7) [ http://www.ncbi.nlm.nih.gov/pubmed/27338657?dopt=AbstractPlus ] – Mouse Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6975  (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/23063522?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10326  (Positive) (pEC 50  5.9) [ http://www.ncbi.nlm.nih.gov/pubmed/23448715?dopt=AbstractPlus ] Comments SANT‐3 and SANT‐4 are SMO antagonists [ http://www.ncbi.nlm.nih.gov/pubmed/12391318?dopt=AbstractPlus ].\nThere is limited knowledge about WNT/FZD specificity and which molecular entities determine the signalling outcome of a specific WNT/FZD pair. Understanding of theFZD and SMO coupling to G proteins is incomplete, but progress have been made [ http://www.ncbi.nlm.nih.gov/pubmed/27458145?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24032637?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24873871?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26179037?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16885213?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23292797?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22179044?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30514810?dopt=AbstractPlus ]. There is also a scarcity of information on basic pharmacological characteristics of FZDs, such as binding constants, ligand specificity or concentration‐response relationships [ http://www.ncbi.nlm.nih.gov/pubmed/19208479?dopt=AbstractPlus ]. Development of pharmacological tools for SMO has been faciliated by successful crystalization of several SMO structures [ http://www.ncbi.nlm.nih.gov/pubmed/27437577?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/29804838?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25008467?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23636324?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24525480?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28513578?dopt=AbstractPlus ]. The recently solved FZD4 in apo state has provided first insight into FZD transmembranous organization [ http://www.ncbi.nlm.nih.gov/pubmed/30135577?dopt=AbstractPlus ].\nWNTs :  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3672  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12774 ,  http://www.uniprot.org/uniprot/P04628 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3673  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12780 ,  http://www.uniprot.org/uniprot/P09544 ) (also known as Int‐1‐related protein),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3674  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12781 ,  http://www.uniprot.org/uniprot/Q93097 ) (also known as WNT‐13),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3675  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12782 ,  http://www.uniprot.org/uniprot/P56703 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3549  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15983 ,  http://www.uniprot.org/uniprot/P56704 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3547  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12783 ,  http://www.uniprot.org/uniprot/P56705 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3548  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12784 ,  http://www.uniprot.org/uniprot/P41221 ) (pEC50 7.7‐8.9 [ http://www.ncbi.nlm.nih.gov/pubmed/30514810?dopt=AbstractPlus ]),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3676  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16265 ,  http://www.uniprot.org/uniprot/Q9H1J7 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3678  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12785 ,  http://www.uniprot.org/uniprot/Q9Y6F9 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3679  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12786 ,  http://www.uniprot.org/uniprot/O00755 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12787 ,  http://www.uniprot.org/uniprot/P56706 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3682  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12788 ,  http://www.uniprot.org/uniprot/Q9H1J5 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3683  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12789 ,  http://www.uniprot.org/uniprot/Q93098 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3684  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12778 ,  http://www.uniprot.org/uniprot/O14904 ) (also known as WNT‐14),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3686  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12779 ,  http://www.uniprot.org/uniprot/O14905 ) (also known as WNT‐15 or WNT14b),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3687 ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13829 ,  http://www.uniprot.org/uniprot/Q9GZT5 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3688  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12775 ,  http://www.uniprot.org/uniprot/O00744 ) (also known as WNT‐12),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3689  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12776 ,  http://www.uniprot.org/uniprot/O96014 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3690  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16267 ,  http://www.uniprot.org/uniprot/Q9UBV4 ).\nExtracellular proteins that interact with FZDs : \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1063  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7678 ,  http://www.uniprot.org/uniprot/Q00604 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3700  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16175 ,  http://www.uniprot.org/uniprot/Q2I0M5 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3691  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10776 ,  http://www.uniprot.org/uniprot/Q8N474 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3692  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10777 ,  http://www.uniprot.org/uniprot/Q96HF1 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3693  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3959 , http://www.uniprot.org/uniprot/Q92765 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3694  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10778 ,  http://www.uniprot.org/uniprot/Q6FHJ7 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3695  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10779 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10779 ).\nExtracellular proteins that interact with WNTs or LRPs: \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3701  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2891 ,  http://www.uniprot.org/uniprot/O94907 ),  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18081  ( http://www.uniprot.org/uniprot/Q9Y5W5 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3704  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13771 ,  http://www.uniprot.org/uniprot/Q9BQB4 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3702  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17550 ,  http://www.uniprot.org/uniprot/Q96MU8 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3703  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18797 ,  http://www.uniprot.org/uniprot/Q8NCW0 )\nSmall exogenous ligands:  Foxy‐5 [ http://www.ncbi.nlm.nih.gov/pubmed/18927296?dopt=AbstractPlus ], Box‐5 [ http://www.ncbi.nlm.nih.gov/pubmed/19901340?dopt=AbstractPlus ], UM206 [ http://www.ncbi.nlm.nih.gov/pubmed/21931076?dopt=AbstractPlus ], and XWnt8 ( http://www.uniprot.org/uniprot/P28026 ) also known as mini‐Wnt8.\nLigands associated with SMO signalling: \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2718 , oxysterols [ http://www.ncbi.nlm.nih.gov/pubmed/27437577?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27705744?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30340023?dopt=AbstractPlus ].\nAngers S  et al . (2009) Proximal events in Wnt signal transduction.  Nat. Rev. Mol. Cell Biol. \n 10 : [ https://www.ncbi.nlm.nih.gov/pubmed/22935904?dopt=AbstractPlus ]\nvan Amerongen R. (2012) Alternative Wnt pathways and receptors.  Cold Spring Harb Perspect Biol \n 4 : 468‐77 [ https://www.ncbi.nlm.nih.gov/pubmed/19536106?dopt=AbstractPlus ]\nSchulte G.(2015)Frizzleds and WNT/β‐cateninsignaling–The black boxof ligand‐receptor selectivity, 113‐39 [ https://www.ncbi.nlm.nih.gov/pubmed/26969975?dopt=AbstractPlus ]\nWang Y  et al . (2016) Frizzled Receptors in Development and Disease.  Curr. Top. Dev. Biol. \n 117 : complex stoichiometry and activation kinetics.  Eur. J. Pharmacol. \n 763 : 191‐5 [ https://www.ncbi.nlm.nih.gov/pubmed/26003275?dopt=AbstractPlus ]\nSchulte G  et al . (2018) Frizzleds as GPCRs ‐ More Conventional Than We Thought!  Trends Pharmacol. Sci. \n 39 : 828‐842 [ https://www.ncbi.nlm.nih.gov/pubmed/30049420?dopt=AbstractPlus ]\n\nComplement peptide receptors ( nomenclature as agreed by the  NC‐IUPHAR  subcommittee on Complement peptide receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/23383423?dopt=AbstractPlus ]) are activated by the endogenous 75 amino‐acid anaphylatoxin polypeptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3640  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ,  http://www.uniprot.org/uniprot/P01024 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=573  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1331 ,  http://www.uniprot.org/uniprot/P01031 ), generated upon stimulation of the complement cascade. C3a and C5a exert their functions through binding to their receptors (C3aR and C5aR), causing cell activation and triggering cellular degranulation that contributes to the local inflammation.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=31 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=32 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=33 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1319 ,  http://www.uniprot.org/uniprot/Q16581 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1338 ,  http://www.uniprot.org/uniprot/P21730 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4527 ,  http://www.uniprot.org/uniprot/Q9P296 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3640  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ,  http://www.uniprot.org/uniprot/P01024 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=573  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1331 ,  http://www.uniprot.org/uniprot/P01031 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8898085?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=573  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1331 ,  http://www.uniprot.org/uniprot/P01031 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=574 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3640  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ,  http://www.uniprot.org/uniprot/P01024 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8898085?dopt=AbstractPlus ] – Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3728  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10402 ,  http://www.uniprot.org/uniprot/P39019 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11107061?dopt=AbstractPlus ] – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9449  [ http://www.ncbi.nlm.nih.gov/pubmed/24257095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8381  [ http://www.ncbi.nlm.nih.gov/pubmed/25259874?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10224  [ http://www.ncbi.nlm.nih.gov/pubmed/9145417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26297549?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10226 \n 2086 ,  http://www.ncbi.nlm.nih.gov/pubmed/26297549?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10227  [ http://www.ncbi.nlm.nih.gov/pubmed/11179594?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7804141?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9746  (Inverse agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/18753409?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=572  [ http://www.ncbi.nlm.nih.gov/pubmed/1732540?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7930622?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10228  [ 2276 ,  http://www.ncbi.nlm.nih.gov/pubmed/26297549?dopt=AbstractPlus ] – Selective agonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9385  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/27108698?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9384  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/27108698?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3529  (pIC 50  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/11342658?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8384  (pIC 50  5.9) [ http://www.ncbi.nlm.nih.gov/pubmed/25259874?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9450  (pIC 50  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/27768695?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=581  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12384495?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9451  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/25385614?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3853  (pIC 50  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9719594?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=576  (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/7930622?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3773 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10092660?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3774 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/4020139?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3774 ) (Agonist) Comments C3a‐C3aR signalling plays a crucial role in inhibiting neural progenitor cell proliferation during neurodevelopment, playing a critical role in the normal development of the mammalian brain [ http://www.ncbi.nlm.nih.gov/pubmed/30449309?dopt=AbstractPlus ]. – –\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3529  has also been reported to have agonist properties at the C3a receptor [ http://www.ncbi.nlm.nih.gov/pubmed/16154494?dopt=AbstractPlus ]. The putative chemoattractant receptor termed C5a 2  (also known as GPR77, C5L2) binds [125I]C5a with no clear signalling function, but has a putative role opposing inflammatory responses [ http://www.ncbi.nlm.nih.gov/pubmed/11773063?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15784721?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15715664?dopt=AbstractPlus ]. Binding to this site may be displaced with the rank order  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=574  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1331 )>  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=573  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1331 ,  http://www.uniprot.org/uniprot/P01031 [ http://www.ncbi.nlm.nih.gov/pubmed/11773063?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12899627?dopt=AbstractPlus ] while there is controversy over the ability of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3640  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ,  http://www.uniprot.org/uniprot/P01024 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5367  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1318 ) to compete [ http://www.ncbi.nlm.nih.gov/pubmed/15990859?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12540846?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15833747?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12899627?dopt=AbstractPlus ]. C5a 2  appears to lack G protein signalling and has been termed a decoy receptor [ http://www.ncbi.nlm.nih.gov/pubmed/19100624?dopt=AbstractPlus ]. However, C5a 2  does recruit arrestin after ligand binding, which might provide a signaling pathway for this receptor [ http://www.ncbi.nlm.nih.gov/pubmed/20044484?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19641221?dopt=AbstractPlus ], and forms heteromers with C5a 1 . C5a, but not C5a‐des Arg, induces upregulation of heteromer formation between complement C5a receptors C5a 1  and C5a 2  [ http://www.ncbi.nlm.nih.gov/pubmed/24060963?dopt=AbstractPlus ]. There are also reports of pro‐inflammatory activity of C5a 2 , mediated by HMGB1, but the signaling pathway that underlies this is currently unclear (reviewed in [ http://www.ncbi.nlm.nih.gov/pubmed/23239822?dopt=AbstractPlus ]). More recently, work in T cells has shown that C5a 1  and C5a 2  act in opposition to each other and that altering the equilibrium between the two receptors, by differential expression or production of C5a‐des Arg (which favours C5a 2 ), can affect the final cellular response [ http://www.ncbi.nlm.nih.gov/pubmed/27313051?dopt=AbstractPlus ].\nArbore G  et al . (2016) A novel \"complement‐metabolism‐inflammasome axis\" as a key regulator of immune cell effector function.  Eur. J. Immunol. \n 46 : 1563‐73 [ https://www.ncbi.nlm.nih.gov/pubmed/27184294?dopt=AbstractPlus ]\nCoulthard LG  et al . (2018) Complement C3a receptor modulates embryonic neural progenitor cell proliferation and cognitive performance.  Mol. Immunol. \n 101 : 176‐181 [ https://www.ncbi.nlm.nih.gov/pubmed/30449309?dopt=AbstractPlus ]\nLaumonnier Y  et al . (2017) Novel insights into the expression pattern of anaphylatoxin receptors in mice and men.  Mol. Immunol. \n 89 : 44‐58 [ https://www.ncbi.nlm.nih.gov/pubmed/28600003?dopt=AbstractPlus ]\nLi R  et al . (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a.  FASEB J. \n 27 : 855‐64 [ https://www.ncbi.nlm.nih.gov/pubmed/23239822?dopt=AbstractPlus ]\nMonk PN  et al . (2007) Function, structure and therapeutic potential of complement C5a receptors.  Br. J. Pharmacol. \n 152 : 429‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/17603557?dopt=AbstractPlus ]\nReichhardt MP  et al . (2018) Intracellular complement activation‐An alarm raising mechanism?  Semin. Immunol. \n 38 : 54‐62 [ https://www.ncbi.nlm.nih.gov/pubmed/29631809?dopt=AbstractPlus ]\n\nCorticotropin‐releasing factor (CRF,  nomenclature as agreed by the  NC‐IUPHAR  subcommittee on Corticotropin‐releasing Factor Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/12615952?dopt=AbstractPlus ]) receptors are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=912  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2355 ,  http://www.uniprot.org/uniprot/P06850 ), a 41 aminoacid peptide,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=919  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12516 ,  http://www.uniprot.org/uniprot/P55089 ), 40 amino‐acids,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=921  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18414 ,  http://www.uniprot.org/uniprot/Q96RP3 ), 38 amino‐acids and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=928  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17781 ,  http://www.uniprot.org/uniprot/Q969E3 ), 38 amino‐acids. CRF 1  and CRF 2  receptors are activated non‐selectively by CRH and UCN. CRF 2  receptors are selectively activated by UCN2 and UCN3. Binding to CRF receptors can be conducted using radioligands [ 125 I]Tyr 0 ‐CRF or [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5389 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5389  with  K \n d  values of 0.1‐0.4 nM. CRF 1  and CRF 2  receptors are non‐selectively antagonized by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=923 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3865 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=925 . CRF 1  receptors are selectively antagonized by small molecules  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3512 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3520 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3489 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3495 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3496 . CRF 2  receptors are selectively antagonized by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=931  and astressin 2B.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=212 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=213 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2357 ,  http://www.uniprot.org/uniprot/P34998 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2358 ,  http://www.uniprot.org/uniprot/Q13324 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=919  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12516 ,  http://www.uniprot.org/uniprot/P55089 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15450949?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11123370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8612563?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=912  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2355 ,  http://www.uniprot.org/uniprot/P06850 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7692441?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9326293?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11123370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9851694?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7477349?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=921  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18414 ,  http://www.uniprot.org/uniprot/Q96RP3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15450949?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=928  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17781 ,  http://www.uniprot.org/uniprot/Q969E3 ) http://www.uniprot.org/uniprot/Q969E3 ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3533  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11907190?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=925  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/24269930?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=925  (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12361401?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3495  (pIC 50  9.3–10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8874139?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3499  (p K \n i  8.3–9) [ http://www.ncbi.nlm.nih.gov/pubmed/10669572?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3512  (p K i 8.3–9) [ http://www.ncbi.nlm.nih.gov/pubmed/8893829?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3520  (p K \n i  8.3–9) [ http://www.ncbi.nlm.nih.gov/pubmed/10867111?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3489  (p K \n i  8.3–9) [ http://www.ncbi.nlm.nih.gov/pubmed/8940412?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3496  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/18288792?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3498  (pIC 50  6.4–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10357258?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=931  (p K \n d  8.8–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/11123370?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3891  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12110614?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10335  (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/12361401?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3890  (p K \n i  8.7–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11835994?dopt=AbstractPlus ]\nA CRF binding protein has been identified ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2356 ,  http://www.uniprot.org/uniprot/P24387 ) to which both  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=912  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2355 ,  http://www.uniprot.org/uniprot/P06850 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=919  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12516 ,  http://www.uniprot.org/uniprot/P55089 ) bind with high affinities, which has been suggested to bind and inactivate circulating  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=912 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2355 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7595134?dopt=AbstractPlus ].\nDeussing JM  et al . (2018) The Corticotropin‐Releasing Factor Family: Physiology of the Stress Response.  Physiol. Rev. \n 98 : 2225‐2286 [ https://www.ncbi.nlm.nih.gov/pubmed/30109816?dopt=AbstractPlus ]\nHauger RL  et al . (2003) International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin‐releasing factor and their ligands.  Pharmacol Rev. \n 55 : 21‐26 [ https://www.ncbi.nlm.nih.gov/pubmed/12615952?dopt=AbstractPlus ]\nGrammatopoulos DK. (2012) Insights into mechanisms of corticotropin‐releasing hormone receptor signal transduction.  Br. J. Pharmacol. \n 166 : 85‐97 [ https://www.ncbi.nlm.nih.gov/pubmed/21883143?dopt=AbstractPlus ]\nLiapakis G  et al . (2011) Members of CRF family and their receptors: from past to future.  Curr. Med. Chem. \n 18 : 2583‐600 [ https://www.ncbi.nlm.nih.gov/pubmed/21568890?dopt=AbstractPlus ]\nSlater PG  et al . (2016) Corticotropin‐Releasing Factor Receptors and Their Interacting Proteins: Functional Consequences.  Mol. Pharmacol. \n 90 : 627‐632 [ https://www.ncbi.nlm.nih.gov/pubmed/27612874?dopt=AbstractPlus ]\nZelenay V  et al . (2017) Structures of the First Extracellular Domain of CRF Receptors.  Curr Mol Pharmacol \n 10 : 318‐324 [ https://www.ncbi.nlm.nih.gov/pubmed/28103782?dopt=AbstractPlus ]\n\nDopamine receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Dopamine Receptors  [ 1906 ]) are commonly divided into D 1 ‐like (D 1  and D5) and D 2 ‐like (D 2 , D 3  and D4) families, where the endogenous agonist is  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940 .\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=214 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=214 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=215 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=215 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3020 ,  http://www.uniprot.org/uniprot/P21728 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3023 ,  http://www.uniprot.org/uniprot/P14416 \n Sub/family‐selective labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=945  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/2144334?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=946  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/2168520?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3300  (Antagonist) (p K \n d  10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/2974511?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10882389?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20122961?dopt=AbstractPlus ] – Rat Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7525564?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=939  [ http://www.ncbi.nlm.nih.gov/pubmed/7525564?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=941  [ http://www.ncbi.nlm.nih.gov/pubmed/12086487?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=37  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=34  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/23279866?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=35  [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8369  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/24755247?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7295  [ http://www.ncbi.nlm.nih.gov/pubmed/9057850?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=33  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=953  [ http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7124  [ http://www.ncbi.nlm.nih.gov/pubmed/22711801?dopt=AbstractPlus ] Sub/family‐selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6077  [ http://www.ncbi.nlm.nih.gov/pubmed/16318870?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=935  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7525564?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2  [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8967990?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1975644?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1840645?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8443  (Biased agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/25660762?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9637  [ http://www.ncbi.nlm.nih.gov/pubmed/17067639?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=938  [ http://www.ncbi.nlm.nih.gov/pubmed/1973652?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3949  [ http://www.ncbi.nlm.nih.gov/pubmed/15980060?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=948  (p K \n i  7–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7525564?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7670  (p K \n i  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15686911?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7557  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/1586393?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=209  (p K i 8.9–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/12629531?dopt=AbstractPlus , 1920],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=96  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9430133?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7556  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/1060115?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=214  (p K \n i  8.9–9) [ http://www.ncbi.nlm.nih.gov/pubmed/12629531?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9015795?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=50  (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9430133?dopt=AbstractPlus ] Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=943  (p K \n i  7.4–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7525564?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=944  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3304  (p K i 8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7862709?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=86  (p K \n i  7.4–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7907989?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7862709?dopt=AbstractPlus ] Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=177  (p K \n i  7.9–8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/17095222?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8642550?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=965  (p K \n i  7.9–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=94  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/7473180?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8368  (p K \n i  7) [ http://www.ncbi.nlm.nih.gov/pubmed/24260782?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24666157?dopt=AbstractPlus ] Labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3299  (Antagonist) (p K \n d  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/4015674?dopt=AbstractPlus ] – Rat \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=216 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=216 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=217 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=217 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=218 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=218 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3024 ,  http://www.uniprot.org/uniprot/P35462 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3025 ,  http://www.uniprot.org/uniprot/P21917 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3026 ,  http://www.uniprot.org/uniprot/P21918 \n Sub/family‐selective labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3300  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/7777184?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1840645?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=946  (Antagonist) (p K \n d  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8051291?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1975644?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/1840645?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=953  [ http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=35  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7295  [ http://www.ncbi.nlm.nih.gov/pubmed/9057850?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=33  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=33  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ] – Sub/family‐selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2  [ http://www.ncbi.nlm.nih.gov/pubmed/7576010?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7664822?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7473180?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8967990?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1975644?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1840645?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2  [ http://www.ncbi.nlm.nih.gov/pubmed/12388666?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8967990?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1840645?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6077  [ http://www.ncbi.nlm.nih.gov/pubmed/16318870?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=952  [ http://www.ncbi.nlm.nih.gov/pubmed/8531103?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7756621?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=975  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15448188?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3301  [ http://www.ncbi.nlm.nih.gov/pubmed/16153699?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3301 ] – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7556  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=98  (p K \n i  8–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9430133?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8935801?dopt=AbstractPlus ,  1920 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7279  (p K \n i  8.4) [ 79 ], (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=958  (p K \n i  6.7–7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301592?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=205  (p K \n i  7.7) [ 1920 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=965  (p K \n i  7.1–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7281  (p K \n i  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/16135699?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7556  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9577836?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=98  (p K \n i  7.8–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16135699?dopt=AbstractPlus ,  1920 ,  http://www.ncbi.nlm.nih.gov/pubmed/9015795?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=980  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9098699?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=205  (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9015795?dopt=AbstractPlus ] – Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=86  (p K \n i  7.5–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/8301582?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18308814?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1354163?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7862709?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=86  (p K \n i  8.7–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/8102973?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18308814?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7862709?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=943  (p K \n i  7.5–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=944  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3304  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/1826762?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=129  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10869410?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=44  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8531087?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6675  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/17672446?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6674  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/17627675?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=143  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/10945872?dopt=AbstractPlus ], ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=955  (p K \n i  6.9–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/7988633?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7473180?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3303  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8642550?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8441  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/15992586?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3302  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8642551?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8440  (p K \n i  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/25221667?dopt=AbstractPlus ] – Selective allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7694  (Negative) (p K i ∼9) [ http://www.ncbi.nlm.nih.gov/pubmed/25583363?dopt=AbstractPlus ] – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3300  (Antagonist) (p K \n d  9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10882389?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20122961?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3296  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7759603?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3298  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7674830?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3295  (Antagonist) (p K \n d  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/8967990?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3297  (Antagonist) (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9262371?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=945  (Antagonist) (p K \n d  9.1)\nThe selectivity of many of these agents is less than two orders of magnitude. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3299  exhibits similar high affinity for D 2  and D 3  receptors (low affinity for D4), but has been used to label D 2  receptors in the presence of a D 3 ‐selective antagonist. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3296  has similar affinity for D 2  and D 3  receptors, but labels only D 3  receptors in the absence of divalent cations. The pharmacological profile of the D5 receptor is similar to, yet distinct from, that of the D 1  receptor. The splice variants of the D 2  receptor are commonly termed D 2 S and D 2 L (short and long). The  DRD4  gene encoding the D4 receptor is highly polymorphic in humans, with allelic variations of the protein from amino acid 387 to 515.\nBeaulieu JM  et al . (2015) Dopamine receptors ‐ IUPHAR Review 13.  Br. J. Pharmacol. \n 172 : 1‐23 [ https://www.ncbi.nlm.nih.gov/pubmed/25671228?dopt=AbstractPlus ]\nBeaulieu JM  et al . (2011) The physiology, signaling, and pharmacology of dopamine receptors.  Pharmacol. Rev. \n 63 : 182‐217 [ https://www.ncbi.nlm.nih.gov/pubmed/21303898?dopt=AbstractPlus ]\nCumming P. (2011) Absolute abundances and affinity states of dopamine receptors in mammalian brain: A review.  Synapse \n 65 : 892‐909 [ https://www.ncbi.nlm.nih.gov/pubmed/21308799?dopt=AbstractPlus ]\nMaggio R  et al . (2010) Dopamine D2‐D3 receptor heteromers: pharmacological properties and therapeutic significance.  Curr Opin Pharmacol \n 10 : 100‐7 [ https://www.ncbi.nlm.nih.gov/pubmed/19896900?dopt=AbstractPlus ]\nPtácek R  et al . (2011) Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders.  Med. Sci. Monit. \n 17 : RA215‐20 [ https://www.ncbi.nlm.nih.gov/pubmed/21873960?dopt=AbstractPlus ]\nSchwartz J‐C  et al . (1998) Dopamine Receptors.  In The IUPHAR Compendium of Receptor Characterization and Classification  Edited by Girdlestone D: IUPHAR Media: 141‐151\nUndieh AS. (2010) Pharmacology of signaling induced by dopamine D(1)‐like receptor activation.  Pharmacol. Ther. \n 128 : 37‐60 [ https://www.ncbi.nlm.nih.gov/pubmed/20547182?dopt=AbstractPlus ]\n\nEndothelin receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Endothelin Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/12037137?dopt=AbstractPlus ]) are activated by the endogenous 21 amino‐acid peptides endothelins 1‐3 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3176 ,  http://www.uniprot.org/uniprot/P05305 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3177 ,  http://www.uniprot.org/uniprot/P20800 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1004  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3178 ,  http://www.uniprot.org/uniprot/P14138 )).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=219 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=220 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3179 ,  http://www.uniprot.org/uniprot/P25101 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3180 ,  http://www.uniprot.org/uniprot/P24530 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3176 ,  http://www.uniprot.org/uniprot/P05305 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3177 ,  http://www.uniprot.org/uniprot/P20800 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1004  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3178 ,  http://www.uniprot.org/uniprot/P14138 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7647976?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3176 ,  http://www.uniprot.org/uniprot/P05305 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3177 ,  http://www.uniprot.org/uniprot/P20800 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1004  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3178 ,  http://www.uniprot.org/uniprot/P14138 ) [ http://www.ncbi.nlm.nih.gov/pubmed/2175397?dopt=AbstractPlus ] Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1008  [ http://www.ncbi.nlm.nih.gov/pubmed/8587419?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8904635?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3859  [ http://www.ncbi.nlm.nih.gov/pubmed/7733918?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3837 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3837  [ http://www.ncbi.nlm.nih.gov/pubmed/1472961?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3886  [ http://www.ncbi.nlm.nih.gov/pubmed/1320877?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3528  (p K \n B  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8201588?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3913  (p A \n 2  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7780649?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3494  (p A \n 2  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8035319?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3528  (p K \n B  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8201588?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3913  (p A \n 2  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7780649?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3494  (p K i 7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/12502366?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7352  (pIC 50  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/22862294?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3950  (p A \n 2  8) [ http://www.ncbi.nlm.nih.gov/pubmed/9171878?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=998  (Inverse agonist) (pIC 50  7.3–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/7647976?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=997  (p A \n 2  6.9–7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7647976?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3951  (p A \n 2  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15139756?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9651  (pIC 50  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/28805809?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1009  (p K \n d  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10479298?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1010  (p K \n d  7.9–8) [ http://www.ncbi.nlm.nih.gov/pubmed/8904635?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3887  (p K \n d  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8904635?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1011  (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8612786?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1002  (Antagonist) (p K \n d  9.6–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9489609?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3479  (Antagonist) (p K \n d  9.2), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1001  (Antagonist) (p K \n d  9–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8012722?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1003  (Antagonist) (p K \n d  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/7768260?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1007  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8301559?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1005  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8587429?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1472961?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7881728?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3760 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3760  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1472961?dopt=AbstractPlus ]\nSplice variants of the ET A  receptor have been identified in rat pituitary cells; one of these, ET A R‐C13, appeared to show loss of function with comparable plasma membrane expression to wild type receptor [ http://www.ncbi.nlm.nih.gov/pubmed/17312275?dopt=AbstractPlus ]. Subtypes of the ET B  receptor have been proposed, although gene disruption studies in mice suggest that only a single gene product exists [ http://www.ncbi.nlm.nih.gov/pubmed/9113361?dopt=AbstractPlus ]. Crystal structures of the ETB receptor bound to the antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3494  and ET B  selective analogue  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9651  [ http://www.ncbi.nlm.nih.gov/pubmed/28805809?dopt=AbstractPlus ] and selective ET B  agonists  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1004  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3178 ,  http://www.uniprot.org/uniprot/P14138 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3886  [ http://www.ncbi.nlm.nih.gov/pubmed/30413709?dopt=AbstractPlus ] have been reported.\nClozel M  et al . (2013) Endothelin receptor antagonists.  Handb Exp Pharmacol \n 218 : 199‐227  https://www.ncbi.nlm.nih.gov/pubmed/24092342?dopt=AbstractPlus\nDavenport AP. (2002) International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature.  Pharmacol. Rev. \n 54 : 219‐26  https://www.ncbi.nlm.nih.gov/pubmed/12037137?dopt=AbstractPlus\nDavenport AP  et al . (2016) Endothelin.  Pharmacol. Rev. \n 68 : 357‐418  https://www.ncbi.nlm.nih.gov/pubmed/26956245?dopt=AbstractPlus\nDavenport AP  et al . (2018) New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine.  Physiol Res \n 67 : S37‐S54  https://www.ncbi.nlm.nih.gov/pubmed/29947527?dopt=AbstractPlus\nMaguire JJ  et al . (2014) Endothelin@25 ‐ new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12.  Br. J. Pharmacol. \n 171 : 5555‐72  https://www.ncbi.nlm.nih.gov/pubmed/25131455?dopt=AbstractPlus\n\nThe G protein‐coupled estrogen receptor (GPER,  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the G protein‐coupled estrogen receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus ]) was identified following observations of estrogen‐evoked  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2352  signalling in breast cancer cells [ http://www.ncbi.nlm.nih.gov/pubmed/8078914?dopt=AbstractPlus ], which mirrored the differential expression of an orphan 7‐transmembrane receptor GPR30 [ http://www.ncbi.nlm.nih.gov/pubmed/9367686?dopt=AbstractPlus ]. There are observations of both cell‐surface and intracellular expression of the GPER receptor [ http://www.ncbi.nlm.nih.gov/pubmed/15705806?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15539556?dopt=AbstractPlus ]. Selective agonist/ antagonists for GPER have been characterized [ http://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus ]. Antagonists of the nuclear estrogen receptor, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1015  [ http://www.ncbi.nlm.nih.gov/pubmed/11043579?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1016  [ http://www.ncbi.nlm.nih.gov/pubmed/15705806?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15539556?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2820  [ http://www.ncbi.nlm.nih.gov/pubmed/24379833?dopt=AbstractPlus ], as well as the flavonoid ’phytoestrogens’  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2826  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5346  [ http://www.ncbi.nlm.nih.gov/pubmed/15090535?dopt=AbstractPlus ], are agonists of GPER. A complete review of GPER pharmacology has been recently published [ http://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus ]. The roles of GPER in physiological systems throughout the body (cardiovascular, metabolic, endocrine, immune, reproductive) and in cancer have also been reviewed [ http://www.ncbi.nlm.nih.gov/pubmed/28595943?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28249728?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28343901?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26189910?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=221 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4485 ,  http://www.uniprot.org/uniprot/Q99527 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1015  [ http://www.ncbi.nlm.nih.gov/pubmed/15539556?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2820  [ http://www.ncbi.nlm.nih.gov/pubmed/24379833?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2817  [ http://www.ncbi.nlm.nih.gov/pubmed/15705806?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1014  [ http://www.ncbi.nlm.nih.gov/pubmed/16520733?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6480  (pIC 50  6.8–6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/21782022?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3320  (pIC 50  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/19430488?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1012  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15539556?dopt=AbstractPlus ]\nAntagonists at the nuclear estrogen receptor, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1015 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1016  [ http://www.ncbi.nlm.nih.gov/pubmed/11043579?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2820  [ http://www.ncbi.nlm.nih.gov/pubmed/24379833?dopt=AbstractPlus ], as well as the flavonoid ‘phytoestrogens’  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2826  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5346  [ http://www.ncbi.nlm.nih.gov/pubmed/15090535?dopt=AbstractPlus ], are agonists at GPER receptors. A complete review of GPER pharmacology has been recently published [ http://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus ].\nBarton M  et al . (2018) Twenty years of the G protein‐coupled estrogen receptor GPER: Historical and personal perspectives.  J. Steroid Biochem. Mol. Biol. \n 176 : 4‐15  https://www.ncbi.nlm.nih.gov/pubmed/28347854?dopt=AbstractPlus\nGaudet HM  et al . (2015) The G‐protein coupled estrogen receptor, GPER: The inside and inside‐out story.  Mol. Cell. Endocrinol. \n 418 Pt 3 : 207‐19  https://www.ncbi.nlm.nih.gov/pubmed/26190834?dopt=AbstractPlus\nProssnitz ER  et al . (2015) International Union of Basic and Clinical Pharmacology. XCVII. G Protein‐Coupled Estrogen Receptor and Its Pharmacologic Modulators.  Pharmacol. Rev. \n 67 : 505‐40  https://www.ncbi.nlm.nih.gov/pubmed/26023144?dopt=AbstractPlus\nProssnitz ER  et al . (2015) What have we learned about GPER function in physiology and disease from knockout mice?  J. Steroid Biochem. Mol. Biol. \n 153 : 114‐26  https://www.ncbi.nlm.nih.gov/pubmed/26189910?dopt=AbstractPlus\n\nThe  http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00510000502765  ( nomenclature agreed by the  NC‐IUPHAR  Subcommittee on the formylpeptide receptor family  [ http://www.ncbi.nlm.nih.gov/pubmed/19498085?dopt=AbstractPlus ]) respond to exogenous ligands such as the bacterial product  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1022  (fMLP) and endogenous ligands such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1031  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:533 ,  http://www.uniprot.org/uniprot/P04083 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3570  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2532 ,  http://www.uniprot.org/uniprot/P08311 ), amyloid β42, serum amyloid A and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1026 , derived from  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5370  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4827 ,  http://www.uniprot.org/uniprot/P68871 ).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=222 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=223 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=224 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3826 ,  http://www.uniprot.org/uniprot/P21462 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3827 ,  http://www.uniprot.org/uniprot/P25090 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3828 ,  http://www.uniprot.org/uniprot/P25089 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1022  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3570  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2532 ,  http://www.uniprot.org/uniprot/P08311 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1031  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:533 ,  http://www.uniprot.org/uniprot/P04083 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12401407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15210802?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3933  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3383  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3402 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1022  [ http://www.ncbi.nlm.nih.gov/pubmed/10393980?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8006586?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8527441?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11141472?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9151906?dopt=AbstractPlus ] – Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034  [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6239  [ http://www.ncbi.nlm.nih.gov/pubmed/22449948?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3933 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3935  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17176 ,  http://www.uniprot.org/uniprot/Q9NRV9 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15623572?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1022  [ http://www.ncbi.nlm.nih.gov/pubmed/7387981?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1262785?dopt=AbstractPlus ] – – Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3383  [ http://www.ncbi.nlm.nih.gov/pubmed/15056011?dopt=AbstractPlus ] – Endogenous antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1026  (pIC 50  4.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11714831?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1373134?dopt=AbstractPlus ] – – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1030  (p K \n i  6–6.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8387097?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1025  (p K \n i  6.1–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8387097?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17082621?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1040  (pIC 50  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15210823?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1030  (pIC 50  4.3–6) [ http://www.ncbi.nlm.nih.gov/pubmed/6280748?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17687636?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10882119?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1018  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/6285921?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3411  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8006586?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1322894?dopt=AbstractPlus ] – Comments A FITC‐conjugated fMLP analogue has been used for binding to the mouse recombinant receptor [ http://www.ncbi.nlm.nih.gov/pubmed/23160941?dopt=AbstractPlus ]. – –\nNote that the data for FPR2/ALX are also reproduced on the  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=35  receptor page.\nDorward DA  et al . (2015) The Role of Formylated Peptides and Formyl Peptide Receptor 1 in Governing Neutrophil Function during Acute Inflammation.  Am. J. Pathol. \n 185 : 1172‐1184  https://www.ncbi.nlm.nih.gov/pubmed/25791526?dopt=AbstractPlus\nDufton N  et al . (2010) Therapeutic anti‐inflammatory potential of formyl‐peptide receptor agonists.  Pharmacol. Ther. \n 127 : 175‐88  https://www.ncbi.nlm.nih.gov/pubmed/20546777?dopt=AbstractPlus\nLiu M  et al . (2012) G protein‐coupled receptor FPR1 as a pharmacologic target in inflammation and human glioblastoma.  Int. Immunopharmacol. \n 14 : 283‐8  https://www.ncbi.nlm.nih.gov/pubmed/22863814?dopt=AbstractPlus\nRabiet MJ  et al . (2011) N‐formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation.  J. Biol. Chem. \n 286 : 26718‐31  https://www.ncbi.nlm.nih.gov/pubmed/21543323?dopt=AbstractPlus\nYazid S  et al . (2012) Anti‐inflammatory drugs, eicosanoids and the annexin A1/FPR2 anti‐inflammatory system.  Prostaglandins Other Lipid Mediat. \n 98 : 94‐100  https://www.ncbi.nlm.nih.gov/pubmed/22123264?dopt=AbstractPlus\nYe RD  et al . (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family.  Pharmacol. Rev. \n 61 : 119‐61  https://www.ncbi.nlm.nih.gov/pubmed/19498085?dopt=AbstractPlus\n\nFree fatty acid receptors (FFA,  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on free fatty acid receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19047536?dopt=AbstractPlus ]) are activated by free fatty acids. Long‐chain saturated and unsaturated fatty acids (including C14.0 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2806 ), C16:0 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055 ), C18:1 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054 ), C18:2 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052 ), C18:3, ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049 ), C20:4 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391 ), C20:5,n‐3 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3362 ) and C22:6,n‐3 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1051 )) activate FFA1 [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565875?dopt=AbstractPlus ] and FFA4 receptors [ http://www.ncbi.nlm.nih.gov/pubmed/15619630?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22343897?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20813258?dopt=AbstractPlus ], while short chain fatty acids (C2 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1058 ), C3 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1062 ), C4 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1059 ) and C5 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1061 )) activate FFA2 [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12684041?dopt=AbstractPlus ] and FFA3 [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ] receptors. The crystal structure for agonist bound FFA1 has been described [ http://www.ncbi.nlm.nih.gov/pubmed/25043059?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=225 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=226 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4498 ,  http://www.uniprot.org/uniprot/O14842 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4501 ,  http://www.uniprot.org/uniprot/O15552 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1051  [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049  [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054  [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2806  [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565875?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1062  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12684041?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1058  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12684041?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1059  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12684041?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6499  [ http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6500  [ http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6485  [ http://www.ncbi.nlm.nih.gov/pubmed/22859723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9148  [ http://www.ncbi.nlm.nih.gov/pubmed/27074625?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6483  [ http://www.ncbi.nlm.nih.gov/pubmed/23687558?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9149  [ http://www.ncbi.nlm.nih.gov/pubmed/22724451?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1050  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16702987?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6484  [ http://www.ncbi.nlm.nih.gov/pubmed/25787200?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24900210?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25043059?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21752941?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10107  [ http://www.ncbi.nlm.nih.gov/pubmed/30247908?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1057  (pIC 50  6) [ http://www.ncbi.nlm.nih.gov/pubmed/16702987?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17200419?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8417  (pIC 50  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/26852904?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25380412?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6487  (pIC 50  6.5) [ http://www.ncbi.nlm.nih.gov/pubmed/23066016?dopt=AbstractPlus ] Comments A wide range of both saturated and unsaturated fatty acids containing from 6 to 22 carbons have been shown to act as agonists at FFA1 [ http://www.ncbi.nlm.nih.gov/pubmed/12496284?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12629551?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12565875?dopt=AbstractPlus ]. Antagonist GW1100 is also an oxytocin receptor antagonist [ http://www.ncbi.nlm.nih.gov/pubmed/16702987?dopt=AbstractPlus ]. Fasiglifam, TUG‐770 and GW9508 are approximately 100 fold selective for FFA1 over FFA4 [ http://www.ncbi.nlm.nih.gov/pubmed/16702987?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23687558?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24900210?dopt=AbstractPlus ]. AMG‐837 and the related analogue AM6331 have been suggested to have an allosteric mechanism of action at FFA1, with respect to the orthosteric fatty acid binding site [ http://www.ncbi.nlm.nih.gov/pubmed/22859723?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23403053?dopt=AbstractPlus ]. – \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=227 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=127 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=228 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4499 ,  http://www.uniprot.org/uniprot/O14843 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19061 ,  http://www.uniprot.org/uniprot/Q5NUL3 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4500 ,  http://www.uniprot.org/uniprot/O15529 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1062  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14722361?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1059  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14722361?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6500  [ http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049  [ http://www.ncbi.nlm.nih.gov/pubmed/22519963?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2806  [ http://www.ncbi.nlm.nih.gov/pubmed/22282525?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049  [ http://www.ncbi.nlm.nih.gov/pubmed/18320172?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054  [ http://www.ncbi.nlm.nih.gov/pubmed/22282525?dopt=AbstractPlus ] – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1058  [ http://www.ncbi.nlm.nih.gov/pubmed/12496283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12711604?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21220428?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14722361?dopt=AbstractPlus ] – – Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8418  [ http://www.ncbi.nlm.nih.gov/pubmed/24997608?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6490  [ http://www.ncbi.nlm.nih.gov/pubmed/22519963?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5587  [ http://www.ncbi.nlm.nih.gov/pubmed/19007110?dopt=AbstractPlus ] – Comments Beta‐hydroxybutyrate has been reported to antagonise FFA3 responses to short chain fatty acids [ http://www.ncbi.nlm.nih.gov/pubmed/21518883?dopt=AbstractPlus ]. A range of FFA3 selective molecules with agonist and antagonist properties, but which bind at sites distinct from the short chain fatty acid binding site ( i.e.  allosteric modulators), have been described [ http://www.ncbi.nlm.nih.gov/pubmed/27385588?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24870406?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26808470?dopt=AbstractPlus ]. A wide range of both saturated and unsaturated fatty acids containing from 6 to 22 carbons have been shown to act as agonists at FFA4 [ http://www.ncbi.nlm.nih.gov/pubmed/25916176?dopt=AbstractPlus ] with a small subset listed above. Compound A [PMID 24997608] exhibits more than 1000 fold selectivity [ http://www.ncbi.nlm.nih.gov/pubmed/24997608?dopt=AbstractPlus ], and TUG‐891 50‐1000 fold selectivity for FFA4 over FFA1 [ http://www.ncbi.nlm.nih.gov/pubmed/22519963?dopt=AbstractPlus ], dependent on the assay. NGC21 exhibits approximately 15 fold selectivity for FFA4 over FFA1 [ http://www.ncbi.nlm.nih.gov/pubmed/20685848?dopt=AbstractPlus ]. –\nShort (361 amino acids) and long (377 amino acids) splice variants of human FFA4 have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/19723586?dopt=AbstractPlus ], which differ by a 16 amino acid insertion in intracellular loop 3, and exhibit differences in intracellular signalling properties in recombinant systems [ http://www.ncbi.nlm.nih.gov/pubmed/22282525?dopt=AbstractPlus ]. The long FFA4 splice variant has not been identified in other primates or rodents to date [ http://www.ncbi.nlm.nih.gov/pubmed/15619630?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19723586?dopt=AbstractPlus ].\nhttps://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:4500  was originally described as a pseudogene within the family ( http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00250000002583 ), but the discovery of several polymorphisms suggests that some versions of GPR42 may be functional [ http://www.ncbi.nlm.nih.gov/pubmed/19630535?dopt=AbstractPlus ].  https://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:4535  is a structurally‐unrelated G protein‐coupled receptor which has been found to respond to medium chain fatty acids [ http://www.ncbi.nlm.nih.gov/pubmed/16966319?dopt=AbstractPlus ].\nBolognini D  et al . (2016) The Pharmacology and Function of Receptors for Short‐Chain Fatty Acids.  Mol. Pharmacol. \n 89 : 388‐98  https://www.ncbi.nlm.nih.gov/pubmed/26719580?dopt=AbstractPlus\nMancini AD  et al . (2013) The fatty acid receptor FFA1/GPR40 a decade later: how much do we know?  Trends Endocrinol. Metab. \n 24 : 398‐407  https://www.ncbi.nlm.nih.gov/pubmed/23631851?dopt=AbstractPlus\nMilligan G  et al . (2017) Complex Pharmacology of Free Fatty Acid Receptors.  Chem. Rev. \n 117 : 67‐110  https://www.ncbi.nlm.nih.gov/pubmed/27299848?dopt=AbstractPlus\nMoniri NH. (2016) Free‐fatty acid receptor‐4 (GPR120): Cellular and molecular function and its role in metabolic disorders.  Biochem. Pharmacol. \n 110‐111 : 1‐15  https://www.ncbi.nlm.nih.gov/pubmed/26827942?dopt=AbstractPlus\nStoddart LA  et al . (2008) International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, ‐2, and ‐3: pharmacology and pathophysiological functions.  Pharmacol. Rev. \n 60 : 405‐17 [ https://www.ncbi.nlm.nih.gov/pubmed/19047536?dopt=AbstractPlus ]\nWatterson KR  et al . (2014) Treatment of type 2 diabetes by free Fatty Acid receptor agonists.  Front Endocrinol (Lausanne) \n 5 : 137 [ https://www.ncbi.nlm.nih.gov/pubmed/25221541?dopt=AbstractPlus ]\n\nFunctional GABA B  receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on GABA B  receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17329545?dopt=AbstractPlus ]) are formed from the heterodimerization of two similar 7TM subunits termed GABA B1  and GABA B2  [ http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17499108?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15451400?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17329545?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17433877?dopt=AbstractPlus ]. GABAB receptors are widespread in the CNS and regulate both pre‐ and postsynaptic activity. The GABA B1  subunit, when expressed alone, binds both antagonists and agonists, but the affinity of the latter is generally 10‐100fold less than for the native receptor. Co‐expression of GABA B1  and GABA B2  subunits allows transport of GABA B1  to the cell surface and generates a functional receptor that can couple to signal transduction pathways such as high‐voltage‐activated Ca 2+  channels (Ca v 2.1, Ca v 2.2), or inwardly rectifying potassium channels (Kir3) [ http://www.ncbi.nlm.nih.gov/pubmed/15269338?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10604925?dopt=AbstractPlus ]. The GABA B1  subunit harbours the GABA (orthosteric)‐binding site within an extracellular domain (ECD) venus flytrap module (VTM), whereas the GABA B2  subunit mediates G protein‐coupled signalling [ http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24305054?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22660477?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15451400?dopt=AbstractPlus ]. The two subunits interact by direct allosteric coupling [ http://www.ncbi.nlm.nih.gov/pubmed/21063387?dopt=AbstractPlus ], such that GABA B2  increases the affinity of GABA B1  for agonists and reciprocally GABA B1  facilitates the coupling of GABA B2  to G proteins [ http://www.ncbi.nlm.nih.gov/pubmed/24305054?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15922585?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15451400?dopt=AbstractPlus ]. GABA B1  and GABA B2  subunits assemble in a 1:1 stoichiometry by means of a coiled‐coil interaction between α‐helices within their carboxy‐termini that masks an endoplasmic reticulum retention motif (RXRR) within the GABA B1  subunit but other domains of the proteins also contribute to their heteromerization [ http://www.ncbi.nlm.nih.gov/pubmed/15269338?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24778228?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15451400?dopt=AbstractPlus ]. Recent evidence indicates that higher order assemblies of GABA B  receptor comprising dimers of heterodimers occur in recombinant expression systems and  in vivo  and that such complexes exhibit negative functional cooperativity between heterodimers [ http://www.ncbi.nlm.nih.gov/pubmed/21552208?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19723778?dopt=AbstractPlus ]. Adding further complexity, KCTD (potassium channel tetramerization proteins) 8, 12, 12b and 16 associate as tetramers with the carboxy terminus of the GABA B2  subunit to impart altered signalling kinetics and agonist potency to the receptor complex [ http://www.ncbi.nlm.nih.gov/pubmed/20406808?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20400944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24836506?dopt=AbstractPlus ] and are reviewed by [ http://www.ncbi.nlm.nih.gov/pubmed/20655485?dopt=AbstractPlus ]. The molecular complexity of GABAB receptors is further increased through association with trafficking and effector proteins [Schwenk et al., 2016, Nature Neuroscience 19(2): 233‐42] and reviewed by [ http://www.ncbi.nlm.nih.gov/pubmed/27905440?dopt=AbstractPlus ]. Four isoforms of the human GABA B1  subunit have been cloned. The predominant GABA B1a  and GABA B1b  isoforms, which are most prevalent in neonatal and adult brain tissue respectively, differ in their ECD sequences as a result of the use of alternative transcription initiation sites. GABA B1a ‐containing heterodimers localise todistal axonsand mediate inhibition of glutamate release in the CA3‐CA1 terminals, and GABA release onto the layer 5 pyramidal neurons, whereas GABA B1b ‐containing receptors occur within dendritic spines and mediate slow postsynaptic inhibition [ http://www.ncbi.nlm.nih.gov/pubmed/16701210?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16701209?dopt=AbstractPlus ]. Only the 1a and 1b variants are identified as components of native receptors [ http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ]. Additional GABA B1  subunit isoforms have been described in rodents and humans [ http://www.ncbi.nlm.nih.gov/pubmed/21124972?dopt=AbstractPlus ] and reviewed by [ http://www.ncbi.nlm.nih.gov/pubmed/15269338?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=242 \n Subunits \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=240 ,  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=241 , http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1919  (Accessory protein),  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1920  (Accessory protein),  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1918  (Accessory protein),  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1917  (Accessory protein) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1082  [ 635 ] – Rat, (‐)‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1064  [ 635 ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1081  [ http://www.ncbi.nlm.nih.gov/pubmed/12663046?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1084  [ http://www.ncbi.nlm.nih.gov/pubmed/12663046?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1080  [ http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1072  (p K \n i  8.5–8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/12663046?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1088  (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1075  (p K \n i  5.5–6) [ http://www.ncbi.nlm.nih.gov/pubmed/12663046?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1069  (p K \n i  4.4) [ http://www.ncbi.nlm.nih.gov/pubmed/11082110?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1068  (pIC 50  4.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9069281?dopt=AbstractPlus ] – Rat Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10267  (Positive) (pEC 50  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/18536733?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5446  (Positive) (p K \n B  4.7) [ http://www.ncbi.nlm.nih.gov/pubmed/29514854?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12954816?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8539  (Negative) (pIC 50  4.4) [ http://www.ncbi.nlm.nih.gov/pubmed/25050158?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1079  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/11641424?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1090  (Antagonist) (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9872315?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3429  (Antagonist) (p K \n d  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10521582?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1076  (Antagonist) (p K \n d  9) [ http://www.ncbi.nlm.nih.gov/pubmed/10692480?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1077  (Antagonist) (p K \n d  9) [ http://www.ncbi.nlm.nih.gov/pubmed/9069281?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3428  (Agonist)\nSubunits \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=240 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=241 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4070 ,  http://www.uniprot.org/uniprot/Q9UBS5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4507 ,  http://www.uniprot.org/uniprot/O75899\nPotencies of agonists and antagonists listed in the table, quantified as IC 50  values for the inhibition of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5381  binding to rat cerebral cortex membranes, are from [ http://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21428811?dopt=AbstractPlus ,  635 ]. Radioligand  K \n D  values relate to binding to rat brain membranes.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1074  is a photoaffinity ligand for the GABA B1  subunit [ http://www.ncbi.nlm.nih.gov/pubmed/10658574?dopt=AbstractPlus ].  CGP27492  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1081 ),  CGP35024  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1080 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1082  act as antagonists at human GABA A \n ρ 1 receptors, with potencies in the low micromolar range [ http://www.ncbi.nlm.nih.gov/pubmed/21428811?dopt=AbstractPlus ]. In addition to the ligands listed in the table,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=707  binds to the VTM of the GABA B1  subunit to act as a positive allosteric modulator of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1067  [ http://www.ncbi.nlm.nih.gov/pubmed/10692480?dopt=AbstractPlus ]. Synthetic positive allosteric modulators with low, or no, intrinsic activity include  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1079 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5446 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5503  [ http://www.ncbi.nlm.nih.gov/pubmed/21181127?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5504  [ http://www.ncbi.nlm.nih.gov/pubmed/17894647?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15269338?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15126507?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21428811?dopt=AbstractPlus ]. The site of action of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1079  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5446  appears to be on the heptahelical domain of the GABA B2  subunit [ http://www.ncbi.nlm.nih.gov/pubmed/16966477?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15451400?dopt=AbstractPlus ]. In the presence of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1079  or  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5446 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1069  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1068  behave as partial agonists [ http://www.ncbi.nlm.nih.gov/pubmed/21428811?dopt=AbstractPlus ]. A negative allosteric modulator of GABA B  activity has been reported [ http://www.ncbi.nlm.nih.gov/pubmed/25050158?dopt=AbstractPlus ]. Knock‐out of the GABA B1  subunit in C57B mice causes the development of severe tonic‐clonic convulsions that prove fatal within a month of birth, whereas GABA B1 \n ‐/‐  BALB/c mice, although also displaying spontaneous epileptiform activity, are viable. The phenotype of the latter animals additionally includes hyperalgesia, hyperlocomotion (in a novel, but not familiar, environment), hyperdopaminergia, memory impairment and behaviours indicative of anxiety [ http://www.ncbi.nlm.nih.gov/pubmed/15451397?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16606363?dopt=AbstractPlus ]. A similar phenotype has been found for GABA B2 \n ‐/‐  BALB/c mice [ http://www.ncbi.nlm.nih.gov/pubmed/15240800?dopt=AbstractPlus ].\nBowery NG  et al . (2002) International Union of Pharmacology. XXXIII. Mammalian gammaaminobutyricacid(B) receptors: structure and function.  Pharmacol Rev. \n 54 : 247‐264 [ https://www.ncbi.nlm.nih.gov/pubmed/12037141?dopt=AbstractPlus ]\nFroestl W. (2011) An historical perspective on GABAergic drugs.  Future Med Chem \n 3 : 163‐75 [ https://www.ncbi.nlm.nih.gov/pubmed/21428811?dopt=AbstractPlus ]\nGassmann M  et al . (2012) Regulation of neuronal GABA(B) receptor functions by subunit composition.  Nat. Rev. Neurosci. \n 13 : 380‐94 [ https://www.ncbi.nlm.nih.gov/pubmed/22595784?dopt=AbstractPlus ]\nPin JP  et al . (2016) Organization and functions of mGlu and GABAB receptor complexes.  Nature \n 540 : 60‐68 [ https://www.ncbi.nlm.nih.gov/pubmed/27905440?dopt=AbstractPlus ]\n\nGalanin receptors ( provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3594  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24840 ,  http://www.uniprot.org/uniprot/Q9UBC7 ). Human  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) is a 30 amino‐acid non‐amidated peptide [ http://www.ncbi.nlm.nih.gov/pubmed/1714839?dopt=AbstractPlus ]; in other species, it is 29 amino acids long and C‐terminally amidated. Amino acids 1–14 of galanin are highly conserved in mammals, birds, reptiles, amphibia and fish. Shorter peptide species ( e.g . human galanin‐1–19 [ http://www.ncbi.nlm.nih.gov/pubmed/1710578?dopt=AbstractPlus ] and porcine galanin‐5–29 [ http://www.ncbi.nlm.nih.gov/pubmed/1283627?dopt=AbstractPlus ]) and N‐terminally extended forms ( e.g.  N‐terminally seven and nine residue elongated forms of porcine galanin [ http://www.ncbi.nlm.nih.gov/pubmed/1718731?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1283627?dopt=AbstractPlus ]) have been reported.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=243 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=244 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=245 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4132 ,  http://www.uniprot.org/uniprot/P47211 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4133 ,  http://www.uniprot.org/uniprot/O43603 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4134 ,  http://www.uniprot.org/uniprot/O60755 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3594  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24840 ,  http://www.uniprot.org/uniprot/Q9UBC7 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10601261?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3594  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24840 ,  http://www.uniprot.org/uniprot/Q9UBC7 ) ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10601261?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3594  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24840 ,  http://www.uniprot.org/uniprot/Q9UBC7 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3592  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4114 ,  http://www.uniprot.org/uniprot/P22466 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15944009?dopt=AbstractPlus ] Agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3876 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9832122?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9742938?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9281594?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9405385?dopt=AbstractPlus ] – Rat – Selective agonists – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3866 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9305929?dopt=AbstractPlus ] – Rat – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3486  (pIC 50  5.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10896115?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3900  (p K \n i  7.9) [ 2010 ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6125  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/16789730?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16730981?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16287967?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6126  (p K \n i  7.8–7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/16789730?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16730981?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16287967?dopt=AbstractPlus ] Selective allosteric modulators – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8547  (Positive) (pEC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/20660766?dopt=AbstractPlus ] – Rat – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5391  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9808667?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5391  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9808667?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5391  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9281594?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6117  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9880084?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9722565?dopt=AbstractPlus ] Comments – The CYM2503 PAM potentiates the anticonvulsant activity of endogenous galanin in mouse seizure models [ http://www.ncbi.nlm.nih.gov/pubmed/20660766?dopt=AbstractPlus ]. –\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5356 ) is a high‐affinity agonist at GAL 1 /GAL 2  (p K i 9), and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5357 ) is selective for GAL 2  and GAL 3  compared with GAL 1  [ http://www.ncbi.nlm.nih.gov/pubmed/15944007?dopt=AbstractPlus ]. [ 125 I]‐[Tyr 26 ]galanin binds to all three subtypes with  K \n d  values generally reported to range from 0.05 to 1 nM, depending on the assay conditions used [ http://www.ncbi.nlm.nih.gov/pubmed/9808667?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2436195?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9305929?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9722565?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9281594?dopt=AbstractPlus ]. Porcine galanin‐(3‐29) does not bind to cloned GAL 1 , GAL 2  or GAL 3  receptors, but a receptor that is functionally activated by porcine galanin‐(3–29) has been reported in pituitary and gastric smooth muscle cells [ http://www.ncbi.nlm.nih.gov/pubmed/7529309?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7683428?dopt=AbstractPlus ]. Additional galanin receptor subtypes are also suggested from studies with chimeric peptides ( e.g .  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3896 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3898  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3899 ), which act as antagonists in functional assays in the cardiovascular system [ http://www.ncbi.nlm.nih.gov/pubmed/7693918?dopt=AbstractPlus ], spinal cord [ http://www.ncbi.nlm.nih.gov/pubmed/1373497?dopt=AbstractPlus ], locus coeruleus, hippocampus [ http://www.ncbi.nlm.nih.gov/pubmed/1720557?dopt=AbstractPlus ] and hypothalamus [ http://www.ncbi.nlm.nih.gov/pubmed/7504301?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1283559?dopt=AbstractPlus ], but exhibit agonist activity at some peripheral sites [ http://www.ncbi.nlm.nih.gov/pubmed/7504301?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7529309?dopt=AbstractPlus ]. The chimeric peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3896 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3897 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3898 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3899  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3861  are agonists at GAL 1  receptors expressed endogenously in Bowes human melanoma cells [ http://www.ncbi.nlm.nih.gov/pubmed/10601261?dopt=AbstractPlus ], and at heterologously expressed recombinant GAL 1 , GAL 2  and GAL 3  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/9808667?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9305929?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9722565?dopt=AbstractPlus ]. Recent studies have described the synthesis of a series of novel, systemically‐active, galanin analogues, with modest preferential binding at the GAL 2  receptor. Specific chemical modifications to the galanin backbone increased brain levels of these peptides after  i.v.  injection and several of these peptides exerted a potent antidepressant‐like effect in mouse models of depression [ http://www.ncbi.nlm.nih.gov/pubmed/23600864?dopt=AbstractPlus ].\nFoord SM  et al . (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57 : 279‐288 [ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nLang R  et al . (2015) Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity.  Pharmacol. Rev. \n 67 : 118‐75 [ https://www.ncbi.nlm.nih.gov/pubmed/25428932?dopt=AbstractPlus ]\nLang R  et al . (2011) The galanin peptide family in inflammation.  Neuropeptides \n 45 : 1‐8 [ https://www.ncbi.nlm.nih.gov/pubmed/21087790?dopt=AbstractPlus ]\nLawrence C  et al . (2011) Galanin‐like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction.  Front Neuroendocrinol \n 32 : 1‐9 [ https://www.ncbi.nlm.nih.gov/pubmed/20558195?dopt=AbstractPlus ]\nWebling KE  et al . (2012) Galanin receptors and ligands.  Front Endocrinol (Lausanne) \n 3 : 146 [ https://www.ncbi.nlm.nih.gov/pubmed/23233848?dopt=AbstractPlus ]\n\nThe ghrelin receptor ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee for the Ghrelin receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/16382107?dopt=AbstractPlus ]) is activated by a 28 amino‐acid peptide originally isolated from rat stomach, where it is cleaved from a 117 aminoacid precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ). The human gene encoding the precursor peptide has 83% sequence homology to rat preproghrelin, although the mature peptides from rat and human differ by only two amino acids [ http://www.ncbi.nlm.nih.gov/pubmed/11549267?dopt=AbstractPlus ]. Alternative splicing results in the formation of a second peptide, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3600  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) with equipotent biological activity [ http://www.ncbi.nlm.nih.gov/pubmed/10801861?dopt=AbstractPlus ]. A unique post‐translational modification (octanoylation of Ser 3 , catalysed by ghrelin  O ‐acyltransferase ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:32311 ,  http://www.uniprot.org/uniprot/Q96T53 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18267071?dopt=AbstractPlus ] occurs in both peptides, essential for full activity in binding to ghrelin receptors in the hypothalamus and pituitary, and for the release of growth hormone from the pituitary [ http://www.ncbi.nlm.nih.gov/pubmed/10604470?dopt=AbstractPlus ]. Structure activity studies showed the first five N‐terminal amino acids to be the minimum required for binding [ http://www.ncbi.nlm.nih.gov/pubmed/11087562?dopt=AbstractPlus ], and receptor mutagenesis has indicated overlap of the ghrelin binding site with those for small molecule agonists and allosteric modulators of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1099  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) function [ http://www.ncbi.nlm.nih.gov/pubmed/18923064?dopt=AbstractPlus ]. In cell systems, the ghrelin receptor is constitutively active [ http://www.ncbi.nlm.nih.gov/pubmed/15383539?dopt=AbstractPlus ], but this is abolished by a naturally occurring mutation (A204E) that results in decreased cell surface receptor expression and is associated with familial short stature [ http://www.ncbi.nlm.nih.gov/pubmed/16511605?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=246 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4267 ,  http://www.uniprot.org/uniprot/Q92847 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1099  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) = [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3600  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12969753?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11549267?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9734  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29571 ,  http://www.uniprot.org/uniprot/Q969E1 ) (pIC 50  8.2) [ 675 ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5870  (pIC 50  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/20593439?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5870  (p K \n B  8) [ http://www.ncbi.nlm.nih.gov/pubmed/21034740?dopt=AbstractPlus ] – Rat Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1094 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11522606?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1096 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11314756?dopt=AbstractPlus ]\n[ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1098  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) has been shown to bind (as [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3810 ) and have effects in the cardiovascular system [ http://www.ncbi.nlm.nih.gov/pubmed/12969753?dopt=AbstractPlus ], which raises the possible existence of different receptor subtypes in peripheral tissues and the central nervous system. A potent inverse agonist has been identified ([ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1102 , p D \n 2  8.3; [ http://www.ncbi.nlm.nih.gov/pubmed/12907757?dopt=AbstractPlus ]).  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3535 , described as a ghrelin receptor agonist (p K i 7.8 and p D \n 2  7.5 at human recombinant ghrelin receptors), has been shown to stimulate ghrelin receptor mediated food intake and gastric emptying but not elicit release of growth hormone, or modify ghrelin stimulated growth hormone release, thus pharmacologically discriminating the orexigenic and gastrointestinal actions of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1099  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18129 ,  http://www.uniprot.org/uniprot/Q9UBU3 ) from the release of growth hormone [ http://www.ncbi.nlm.nih.gov/pubmed/18719021?dopt=AbstractPlus ]. A number of selective antagonists have been reported, including peptidomimetic [ http://www.ncbi.nlm.nih.gov/pubmed/22798076?dopt=AbstractPlus ] and non‐peptide small molecules including  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5870  [ http://www.ncbi.nlm.nih.gov/pubmed/21034740?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20593439?dopt=AbstractPlus ].\nAndrews ZB. (2011) The extra‐hypothalamic actions of ghrelin on neuronal function.  Trends Neurosci. \n 34 : 31‐40 [ https://www.ncbi.nlm.nih.gov/pubmed/21035199?dopt=AbstractPlus ]\nAngelidis G  et al . (2010) Current and potential roles of ghrelin in clinical practice.  J. Endocrinol. Invest. \n 33 : 823‐38 [ https://www.ncbi.nlm.nih.gov/pubmed/21293171?dopt=AbstractPlus ]\nBriggs DI  et al . (2011) Metabolic status regulates ghrelin function on energy homeostasis.  Neuroendocrinology \n 93 : 48‐57 [ https://www.ncbi.nlm.nih.gov/pubmed/21124019?dopt=AbstractPlus ]\nCallaghan B  et al . (2014) Novel and conventional receptors for ghrelin, desacyl‐ghrelin, and pharmacologically related compounds.  Pharmacol. Rev. \n 66 : 984‐1001 [ https://www.ncbi.nlm.nih.gov/pubmed/25107984?dopt=AbstractPlus ]\nDavenport AP  et al . (2005) International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function.  Pharmacol. Rev. \n 57 : 541‐6 [ https://www.ncbi.nlm.nih.gov/pubmed/16382107?dopt=AbstractPlus ]\n\nThe glucagon family of receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the Glucagon receptor family  [ http://www.ncbi.nlm.nih.gov/pubmed/12615957?dopt=AbstractPlus ]) are activated by the endogenous peptide (27‐44 aa) hormones  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1136  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5194  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1140  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ), glucose‐dependent insulinotropic polypeptide (also known as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3542  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4270 ,  http://www.uniprot.org/uniprot/P09681 )),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2270  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4265 ,  http://www.uniprot.org/uniprot/P01286 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10607 ,  http://www.uniprot.org/uniprot/P09683 ). One common precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ) generates  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1136  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5194  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1140  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ) peptides [ http://www.ncbi.nlm.nih.gov/pubmed/11179772?dopt=AbstractPlus ]. For a recent review on review the current understanding of the structures of GLP‐1 and GLP‐1R, the molecular basis of their interaction, and the signaling events associated with it, see de Graaf et al., 2016 [ http://www.ncbi.nlm.nih.gov/pubmed/27630114?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=247 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=248 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=249 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4266 ,  http://www.uniprot.org/uniprot/Q02643 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4271 ,  http://www.uniprot.org/uniprot/P48546 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4324 ,  http://www.uniprot.org/uniprot/P43220 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2270  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4265 ,  http://www.uniprot.org/uniprot/P01286 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3542  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4270 ,  http://www.uniprot.org/uniprot/P09681 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7589426?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1132  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15528268?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3544 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8404634?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6523  [ http://www.ncbi.nlm.nih.gov/pubmed/24373935?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6998 \n – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1133  [ http://www.ncbi.nlm.nih.gov/pubmed/10794683?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7387  [ http://www.ncbi.nlm.nih.gov/pubmed/20570597?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8544  [ http://www.ncbi.nlm.nih.gov/pubmed/25176008?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3857  [ http://www.ncbi.nlm.nih.gov/pubmed/8993400?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6959 \n – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9724  [ http://www.ncbi.nlm.nih.gov/pubmed/26308095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1135  [ http://www.ncbi.nlm.nih.gov/pubmed/18412318?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1135  [ http://www.ncbi.nlm.nih.gov/pubmed/15528268?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3730  ( http://www.uniprot.org/uniprot/P20394 ) [ http://www.ncbi.nlm.nih.gov/pubmed/1704369?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1107  (p K \n i  10.1–10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10542394?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9892695?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14755056?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1109  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10542394?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9892695?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14755056?dopt=AbstractPlus ] – Rat [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3847 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3847  [ http://www.ncbi.nlm.nih.gov/pubmed/12627321?dopt=AbstractPlus ] – Mouse \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1138 ) (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15528268?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6524 ) (pIC 50  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9261127?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=884  (pIC 50  4.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11498540?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3783 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11814616?dopt=AbstractPlus ] – Rat [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1131 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8795084?dopt=AbstractPlus ] – Rat [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1134  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15528268?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1137 ) (Antagonist) (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/15528268?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3784 ) (Agonist) \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=250 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=251 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=252 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4325 ,  http://www.uniprot.org/uniprot/O95838 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4192 ,  http://www.uniprot.org/uniprot/P47871 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10608 ,  http://www.uniprot.org/uniprot/P47872 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1140  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11738243?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1136  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4191 ,  http://www.uniprot.org/uniprot/P01275 ) [ http://www.ncbi.nlm.nih.gov/pubmed/4305077?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10607 ,  http://www.uniprot.org/uniprot/P09683 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7612008?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7049  [ http://www.ncbi.nlm.nih.gov/pubmed/25859983?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9760  [ http://www.ncbi.nlm.nih.gov/pubmed/29300013?dopt=AbstractPlus ] – Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3505  (pIC 50  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10085108?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9479  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/26681715?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25656305?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1150  (p A \n 2  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/3035568?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2560175?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3515  (p K \n i  5) [ http://www.ncbi.nlm.nih.gov/pubmed/9857085?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3491  [ http://www.ncbi.nlm.nih.gov/pubmed/11719833?dopt=AbstractPlus ] [( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3755  (p K \n i  5.3) [ http://www.ncbi.nlm.nih.gov/pubmed/1702423?dopt=AbstractPlus ] Labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3785 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3759 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9843782?dopt=AbstractPlus ] – Rat\nThe glucagon receptor has been reported to interact with receptor activity modifying proteins (RAMPs), specifically  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=52 , in heterologous expression systems [ http://www.ncbi.nlm.nih.gov/pubmed/12446722?dopt=AbstractPlus ], although the physiological significance of this has yet to be established.\nAhrén B. (2019) Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development.  J Diabetes Investig \n 10 : 196‐201 [ https://www.ncbi.nlm.nih.gov/pubmed/30099845?dopt=AbstractPlus ]\nAndersen A  et al . (2018) Glucagon‐like peptide 1 in health and disease.  Nat Rev Endocrinol \n 14 : 390‐403 [ https://www.ncbi.nlm.nih.gov/pubmed/29728598?dopt=AbstractPlus ]\nGentilella R  et al . (2019) Glucagon‐like peptide‐1 receptor agonists in type 2 diabetes treatment: are they all the same?  Diabetes Metab. Res. Rev. \n 35 : e3070 [ https://www.ncbi.nlm.nih.gov/pubmed/30156747?dopt=AbstractPlus ]\nGraaf Cd  et al . (2016) Glucagon‐Like Peptide‐1 and Its Class B G Protein‐Coupled Receptors: A Long March to Therapeutic Successes.  Pharmacol. Rev. \n 68 : 954‐1013 [ https://www.ncbi.nlm.nih.gov/pubmed/27630114?dopt=AbstractPlus ]\nRomera I  et al . (2019) A Review of Practical Issues on the Use of Glucagon‐Like Peptide‐1 Receptor Agonists for the Management of Type 2 Diabetes.  Diabetes Ther \n 10 : 5‐19 [ https://www.ncbi.nlm.nih.gov/pubmed/30506340?dopt=AbstractPlus ]\nTrujillo JM  et al . (2014) GLP‐1 receptor agonists for type 2 diabetes mellitus: recent developments and emerging agents.  Pharmacotherapy \n 34 : 1174‐86 [ https://www.ncbi.nlm.nih.gov/pubmed/25382096?dopt=AbstractPlus ]\nZhang Y  et al . (2017) Cryo‐EM structure of the activated GLP‐1 receptor in complex with a G protein.  Nature \n 546 : 248‐253 [ https://www.ncbi.nlm.nih.gov/pubmed/28538729?dopt=AbstractPlus ]\n\nGlycoprotein hormone receptors ( provisional nomenclature  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by a non‐covalent heterodimeric glycoprotein made up of a common α chain\n( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3731  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 ,  http://www.uniprot.org/uniprot/P01215 )  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 ,  http://www.uniprot.org/uniprot/P01215 ), with a unique β chain that confers the biological specificity to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1157  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3964 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01225 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1159  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6584 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01229 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1160  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1886 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01233 ) or  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3920  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12372 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01222 ). There is binding cross‐reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [ http://www.ncbi.nlm.nih.gov/pubmed/2542111?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=253 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=254 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=255 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3969 ,  http://www.uniprot.org/uniprot/P23945 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6585 ,  http://www.uniprot.org/uniprot/P22888 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12373 ,  http://www.uniprot.org/uniprot/P16473 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1157  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3964 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01225 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1159  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6584 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01229 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1160  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1886 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01233 ) [ http://www.ncbi.nlm.nih.gov/pubmed/1922095?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12727981?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3920  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:1885 \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12372 ,  http://www.uniprot.org/uniprot/P01215 \n http://www.uniprot.org/uniprot/P01222 ) Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3780  (Agonist) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3793  (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3775  (Agonist) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3806  (Agonist)\nJiang X  et al . (2012) Structure of follicle‐stimulating hormone in complex with the entire ectodomain of its receptor.  Proc. Natl. Acad. Sci. U.S.A. \n 109 : 12491‐6  https://www.ncbi.nlm.nih.gov/pubmed/22802634?dopt=AbstractPlus\nKleinau G  et al . TSH receptor mutations and disease.  http://www.thyroidmanager.org/chapter/tsh‐receptor‐mutations‐and‐diseases/ . Accessed on 2017‐02‐23.\nTao YX  et al . (2009) Follicle stimulating hormone receptor mutations and reproductive disorders.  Prog Mol Biol Transl Sci \n 89 : 115‐31  https://www.ncbi.nlm.nih.gov/pubmed/20374735?dopt=AbstractPlus\nTroppmann B  et al . (2013) Structural and functional plasticity of the luteinizing hormone/choriogonadotrophin receptor.  Hum. Reprod. Update \n 19 : 583‐602  https://www.ncbi.nlm.nih.gov/pubmed/23686864?dopt=AbstractPlus\n\nGnRH 1  and GnRH 2  receptors ( provisonal nomenclature  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ], also called Type I and Type II GnRH receptor, respectively [ http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ]) have been cloned from numerous species, most of which express two or three types of GnRH receptor [ http://www.ncbi.nlm.nih.gov/pubmed/16140177?dopt=AbstractPlus ,  http:http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15878963?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) (p‐Glu‐His‐Trp‐Ser‐Tyr‐Gly‐LeuArg‐Pro‐Gly‐NH2) is a hypothalamic decapeptide also known as luteinizing hormone‐releasing hormone, gonadoliberin, luliberin, gonadorelin or simply as GnRH. It is a member of a family of similar peptides found in many species [ http://www.ncbi.nlm.nih.gov/pubmed/16140177?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15878963?dopt=AbstractPlus ] including  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) (pGlu‐His‐Trp‐Ser‐His‐Gly‐Trp‐Tyr‐Pro‐Gly‐NH 2  (which is also known as chicken GnRH‐II). Receptors for three forms of GnRH exist in some species but only GnRH I and GnRH II and their cognate receptors have been found in mammals [ http://www.ncbi.nlm.nih.gov/pubmed/16140177?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15878963?dopt=AbstractPlus ]. GnRH 1  receptors are expressed by pituitary gonadotrophs, where they mediate the effects of GnRH on gonadotropin hormone synthesis and secretion that underpin central control of mammalian reproduction. GnRH analogues are used in assisted reproduction and to treat steroid hormone‐dependent conditions [ http://www.ncbi.nlm.nih.gov/pubmed/12072036?dopt=AbstractPlus ]. Notably, agonists cause desensitization of GnRH‐stimulated gonadotropin secretion and the consequent reduction in circulating sex steroids is exploited to treat hormone‐dependent cancers of the breast, ovary and prostate [ http://www.ncbi.nlm.nih.gov/pubmed/12072036?dopt=AbstractPlus ]. GnRH1 receptors are selectively activated by GnRH I and all lack the COOH‐terminal tails found in other GPCRs. GnRH 2  receptors do have COOH‐terminal tails and (where tested) are selective for GnRH II over GnRH I. GnRH 2  receptors are expressed by some primates but not by humans [ http://www.ncbi.nlm.nih.gov/pubmed/12538601?dopt=AbstractPlus ]. Phylogenetic classifications divide GnRH receptors into three [ http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ] or five groups [ http://www.ncbi.nlm.nih.gov/pubmed/25344287?dopt=AbstractPlus ] and highlight examples of gene loss through evolution, with humans retaining only one ancient gene.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=256 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=257 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4421 ,  http://www.uniprot.org/uniprot/P30968 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16341 ,  http://www.uniprot.org/uniprot/Q96P88 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) (Monkey) [ http://www.ncbi.nlm.nih.gov/pubmed/11493674?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) [ http://www.ncbi.nlm.nih.gov/pubmed/17452338?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) [ http://www.ncbi.nlm.nih.gov/pubmed/19638591?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17452338?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17942747?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11493674?dopt=AbstractPlus ] – Monkey,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11493674?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ] – Monkey Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3860  [ http://www.ncbi.nlm.nih.gov/pubmed/26774084?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3860  [ http://www.ncbi.nlm.nih.gov/pubmed/26398856?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3860  [ http://www.ncbi.nlm.nih.gov/pubmed/26398856?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1177  [ http://www.ncbi.nlm.nih.gov/pubmed/11726197?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1175  [ http://www.ncbi.nlm.nih.gov/pubmed/17095587?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3879 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3902 \n – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3854  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/1850267?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1190  (p K \n i  9.3–10) [ http://www.ncbi.nlm.nih.gov/pubmed/7649152?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9300077?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17095587?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1188  (p K \n i  9.1–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/17095587?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5585  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/21188095?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3877 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3916  [ http://www.ncbi.nlm.nih.gov/pubmed/14651258?dopt=AbstractPlus ] – Monkey Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1186  (Antagonist) (p K \n d  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/10894158?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1168  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9484907?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1167  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8013367?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3786  (Agonist) –\nGnRH 1  and GnRH 2  receptors couple primarily to G q/11  [ http://www.ncbi.nlm.nih.gov/pubmed/10734055?dopt=AbstractPlus ] but coupling to G s  and G i  is evident in some systems [ http://www.ncbi.nlm.nih.gov/pubmed/12591945?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8013367?dopt=AbstractPlus ]. GnRH 2  receptors may also mediate (heterotrimeric) G protein‐independent signalling to protein kinases [ http://www.ncbi.nlm.nih.gov/pubmed/15059960?dopt=AbstractPlus ]. There is increasing evidence for expression of GnRH receptors on hormone‐dependent cancer cells where they can exert antiproliferative and/or proapoptotic effects and mediate effects of cytotoxins conjugated to GnRH analogues [ http://www.ncbi.nlm.nih.gov/pubmed/15561800?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15613448?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14726258?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15350601?dopt=AbstractPlus ]. In some human cancer cell models  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) is more potent than  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ), implying mediation by GnRH 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/12237622?dopt=AbstractPlus ], but GnRH 2  receptors are not expressed by humans because the human GNRHR2 gene contains a frame shift and internal stop codon [ http://www.ncbi.nlm.nih.gov/pubmed/12538601?dopt=AbstractPlus ]. The possibility remains that this gene generates GnRH 2  receptor‐related proteins (other than the full‐length receptor) that mediate responses to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1164  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4420 ,  http://www.uniprot.org/uniprot/O43555 ) (see [ http://www.ncbi.nlm.nih.gov/pubmed/11861490?dopt=AbstractPlus ]). Alternatively, evidence for multiple active GnRH receptor conformations [ http://www.ncbi.nlm.nih.gov/pubmed/15059960?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22808094?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20009083?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15492280?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus ] raises the possibility that GnRH 1  receptor‐mediated proliferation inhibition in hormone‐dependent cancer cells is dependent upon a conformation that couples to G i  rather than G q/11  proteins as in pituitary cells [ http://www.ncbi.nlm.nih.gov/pubmed/22808094?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15492280?dopt=AbstractPlus ]. Loss‐of‐function mutations in the GnRH 1  receptor and deficiency of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1162  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4419 ,  http://www.uniprot.org/uniprot/P01148 ) are associated with hypogonadotropic hypogonadism although some ’loss of function’ mutations may actually prevent trafficking of ’functional’ GnRH 1  receptors to the cell surface, as evidenced by recovery of function by nonpeptide antagonists [ http://www.ncbi.nlm.nih.gov/pubmed/12843188?dopt=AbstractPlus ]. Human GnRH 1  receptors are poorly expressed at the cell surface because of failure to meet structural quality control criteria for endoplasmic reticulum exit [ http://www.ncbi.nlm.nih.gov/pubmed/19888967?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12843188?dopt=AbstractPlus ], and this increases susceptibility to point mutations that further impair trafficking [ http://www.ncbi.nlm.nih.gov/pubmed/19888967?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12843188?dopt=AbstractPlus ]. GnRH receptor signalling may require receptor oligomerisation [ http://www.ncbi.nlm.nih.gov/pubmed/6282571?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11278883?dopt=AbstractPlus ].\nDesaulniers AT  et al . (2017) Expression and Role of Gonadotropin‐Releasing Hormone 2 and Its Receptor in Mammals.  Front Endocrinol (Lausanne) \n 8 : 269  https://www.ncbi.nlm.nih.gov/pubmed/29312140?dopt=AbstractPlus\nLimonta P  et al . (2012) GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies.  Endocr. Rev. \n 33 : 784‐811  https://www.ncbi.nlm.nih.gov/pubmed/22778172?dopt=AbstractPlus\nMcArdle CA and Roberson MS.. (2015) Gonadotropes and gonadotropin‐releasing hormone signaling.  In Knobil and Neill's Physiology of Reproduction (4th edition).  Edited by Plant TM and Zeleznik AJ.: Elsevier Inc.: [ISBN: 9780123971753]\nMillar RP  et al . (2004) Gonadotropin‐releasing hormone receptors.  Endocr Rev \n 25 : 235‐275  https://www.ncbi.nlm.nih.gov/pubmed/15082521?dopt=AbstractPlus\nTao YX  et al . (2014) Chaperoning G protein‐coupled receptors: from cell biology to therapeutics.  Endocr. Rev. \n 35 : 602‐47  https://www.ncbi.nlm.nih.gov/pubmed/24661201?dopt=AbstractPlus\n\nGPR18, GPR55 and GPR119 ( provisional nomenclature ), although showing little structural similarity to CB 1  and CB 2  cannabinoid receptors, respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]. Although there are multiple reports to indicate that GPR18, GPR55 and GPR119 can be activated  in vitro  by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3635 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4028  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2661 , respectively, there is a lack of evidence for activation by these lipid messengers  in vivo . As such, therefore, these receptors retain their orphan status.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=89 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=109 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=126 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4472 ,  http://www.uniprot.org/uniprot/Q14330 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4511 ,  http://www.uniprot.org/uniprot/Q9Y2T6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19060 ,  http://www.uniprot.org/uniprot/Q8TDV5 \n Potency order of endogenous ligands – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2661 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3622  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3621  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2364  is ineffective) [ http://www.ncbi.nlm.nih.gov/pubmed/16517404?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3635  [ http://www.ncbi.nlm.nih.gov/pubmed/16844083?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4028  [ http://www.ncbi.nlm.nih.gov/pubmed/20136841?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17765871?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4029  [ http://www.ncbi.nlm.nih.gov/pubmed/18845565?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2661  [ http://www.ncbi.nlm.nih.gov/pubmed/19901198?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16517404?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3622 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3621 \n Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3317  [ http://www.ncbi.nlm.nih.gov/pubmed/20136841?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19723626?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17876302?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4027  [ http://www.ncbi.nlm.nih.gov/pubmed/20804735?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3319  [ http://www.ncbi.nlm.nih.gov/pubmed/16517404?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3318  [ http://www.ncbi.nlm.nih.gov/pubmed/16517404?dopt=AbstractPlus ] Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6577  (apparent pA 2 ) (p A \n 2  7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/23639801?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9967  (plC 50  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/22091481?dopt=AbstractPlus ] – Comments The pairing of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3635  with GPR18 was not replicated in two studies based on arrestin assays [ http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ]. See [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] for discussion. See reviews [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ] and [ http://www.ncbi.nlm.nih.gov/pubmed/25926795?dopt=AbstractPlus ]. In addition to those shown above, further small molecule agonists have been reported [ http://www.ncbi.nlm.nih.gov/pubmed/26048791?dopt=AbstractPlus ].\nGPR18 failed to respond to a variety of lipid‐derived agents in an  in vitro  screen [ http://www.ncbi.nlm.nih.gov/pubmed/19286662?dopt=AbstractPlus ], but has been reported to be activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424  [ http://www.ncbi.nlm.nih.gov/pubmed/21595653?dopt=AbstractPlus ]. GPR55 responds to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3317  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=743  at micromolar concentrations, compared to their nanomolar affinity as CB 1  receptor antagonists/inverse agonists [ http://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus ]. It has been reported that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4028  acts at other sites in addition to GPR55 [ http://www.ncbi.nlm.nih.gov/pubmed/23714700?dopt=AbstractPlus ]. N‐Arachidonoylserine has been suggested to act as a low efficacy agonist/antagonist at GPR18  in vitro  [ http://www.ncbi.nlm.nih.gov/pubmed/20346144?dopt=AbstractPlus ]. It has also been suggested  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3623  acts, at least in part, through GPR119 [ http://www.ncbi.nlm.nih.gov/pubmed/18724386?dopt=AbstractPlus ]. Although  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3318  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3319  produce GPR119‐dependent responses in heterologous expression systems, comparison with  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2661 ‐mediated responses suggests additional mechanisms of action [ http://www.ncbi.nlm.nih.gov/pubmed/18724386?dopt=AbstractPlus ].\nDavenport AP  et al . (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein‐coupled receptor list: recommendations for new pairings with cognate ligands.  Pharmacol. Rev. \n 65 : 967‐86  https://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus\nHassing HA  et al . (2016) Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119.  Biochem. Pharmacol. \n 119 : 66‐75  https://www.ncbi.nlm.nih.gov/pubmed/27569424?dopt=AbstractPlus\nIrving A  et al . (2017) Cannabinoid Receptor‐Related Orphan G Protein‐Coupled Receptors.  Adv Pharmacol \n 80 : 223‐247  https://www.ncbi.nlm.nih.gov/pubmed/28826536\nLiu B  et al . (2015) GPR55: from orphan to metabolic regulator?  Pharmacol. Ther. \n 145 : 35‐42  https://www.ncbi.nlm.nih.gov/pubmed/24972076?dopt=AbstractPlus\nPertwee RG  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB_1 and CB_2.  Pharmacol. Rev. \n 62 : 588‐631  https://www.ncbi.nlm.nih.gov/pubmed/21079038?dopt=AbstractPlus\n\nHistamine receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Histamine Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/9311023?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ]) are activated by the endogenous ligand  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1204 . Marked species differences exist between histamine receptor orthologues [ http://www.ncbi.nlm.nih.gov/pubmed/9311023?dopt=AbstractPlus ]. The human and rat H 3  receptor genes are subject to significant splice variance [ http://www.ncbi.nlm.nih.gov/pubmed/16415177?dopt=AbstractPlus ]. The potency order of histamine at histamine receptor subtypes is H 3  = H 4  > H 2  > H 1  [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ]. Some agonists at the human H 3  receptor display significant ligand bias [ http://www.ncbi.nlm.nih.gov/pubmed/27864425?dopt=AbstractPlus ]. Antagonists of all 4 histamine receptors have clinical uses: H 1  antagonists for allergies ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1222 ), H 2  antagonists for acid‐reflux diseases ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1234 ), H 3  antagonists for narcolepsy ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8924 /WAKIX; Registered) and H 4  antagonists for atopic dermatitis ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8985 ; Phase IIa) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ] and vestibular neuritis (AUV) (SENS‐111 (Seliforant, previously UR‐63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [ http://www.ncbi.nlm.nih.gov/pubmed/27673668?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30152527?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=262 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=263 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5182 ,  http://www.uniprot.org/uniprot/P35367 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5183 ,  http://www.uniprot.org/uniprot/P25021 \n Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1205  [ http://www.ncbi.nlm.nih.gov/pubmed/12626648?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4026  [ http://www.ncbi.nlm.nih.gov/pubmed/15947036?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4025  [ http://www.ncbi.nlm.nih.gov/pubmed/19072936?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=277  (p K \n i  10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/7925364?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7282  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/16782354?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1227  (Inverse agonist) (p K \n i  8.7–9) [ http://www.ncbi.nlm.nih.gov/pubmed/12065734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15206929?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1222  (Inverse agonist) (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/7925364?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1224  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/12065734?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6063  (p K \n i  10.3) [ 79 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7157  (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/15482930?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1228  (p K \n i  8.5–9) [ http://www.ncbi.nlm.nih.gov/pubmed/12065734?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925364?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7121  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/21381763?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2603  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/12747773?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1235  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9384502?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1234  (p K \n i  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/7921611?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1231  (p K \n i  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/23466604?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1220  (Antagonist, Inverse agonist) (p K \n d  8.4–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9794809?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7925364?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8935801?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12626648?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3958  (Antagonist) (p K \n d  9) [ http://www.ncbi.nlm.nih.gov/pubmed/15093820?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3957  (Antagonist, Inverse agonist) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1230  (Antagonist) (p K \n d  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/8961278?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3959  (Antagonist) (p K \n d  7.7–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12869657?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=264 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=265 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:5184 ,  http://www.uniprot.org/uniprot/Q9Y5N1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17383 ,  http://www.uniprot.org/uniprot/Q9H3N8 \n Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4024  [ http://www.ncbi.nlm.nih.gov/pubmed/15115383?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1254  [ http://www.ncbi.nlm.nih.gov/pubmed/15771452?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7346  (Inverse agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/18598020?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1223  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12606603?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15947036?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11179434?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11561071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11181941?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1269  [ http://www.ncbi.nlm.nih.gov/pubmed/16432504?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15947036?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8983  [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1274  [ http://www.ncbi.nlm.nih.gov/pubmed/17154494?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1266  (p K \n i  8.2–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11714875?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12393057?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8924  (p K \n i  8.1–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19329325?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4023  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/15033391?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8981  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7346  (p K \n i  8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1267  (Selective for H 3 /H 4  compared to H 1  and H 3 .) (p K \n i  7.1–7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11284713?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15294456?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12606603?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11090094?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10869375?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11714875?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12393057?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1265  (p K \n i  6.7–7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11284713?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15294456?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12606603?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11090094?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12393057?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8985  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8982  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1278  (p K \n i  7.8–8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/15947036?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16854056?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14722321?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8984  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24495018?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1267  (Selective for H 3 /H 4  compared to H 1  and H 3 .) (p K \n i  6.3–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15294456?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12606603?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11179434?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11561071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11181941?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11179436?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1264  (Antagonist) (p K \n d  10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/11090094?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3960  (Antagonist) (p K \n d  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/7834183?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1237  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11179434?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1240  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12706455?dopt=AbstractPlus ] – Mouse \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1279  (Antagonist) (p K \n d  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/14722321?dopt=AbstractPlus ]\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4026  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1205  are reduced efficacy agonists. The H 4  receptor appears to exhibit broadly similar pharmacology to the H 3  receptor for imidazole‐containing ligands, although  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1236  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1239  are less potent, while  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1223  acts as a reduced efficacy agonist at the H 4  receptor and an antagonist at the H 3  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/11179434?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11118334?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11179435?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10973974?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11179436?dopt=AbstractPlus ]. Moreover,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1269  is identified as a high affinity, full agonist for the human H 4  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/15947036?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1247  has been used to label the H 4  receptor heterologous expression systems.\nGbahou F  et al . (2012) The histamine autoreceptor is a short isoform of the H_3 receptor.  Br. J. \n Pharmacol. \n 166 : 1860‐71  https://www.ncbi.nlm.nih.gov/pubmed/22356432?dopt=AbstractPlus\nNieto‐Alamilla G  et al . (2016) The Histamine H3 Receptor: Structure, Pharmacology, and Function.  Mol. Pharmacol. \n 90 : 649‐673  https://www.ncbi.nlm.nih.gov/pubmed/27563055?dopt=AbstractPlus\nPanula P  et al . (2015) International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.  Pharmacol. Rev. \n 67 : 601‐55  https://www.ncbi.nlm.nih.gov/pubmed/26084539?dopt=AbstractPlus\nvan Rijn RM  et al . (2008) Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor.  Biochem. J. \n 414 : 121‐31 [ https://www.ncbi.nlm.nih.gov/pubmed/18452403?dopt=AbstractPlus ]\n\nThe hydroxycarboxylic acid family of receptors ( http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00500000271913 ,  nomenclature as agreed by the \n NC‐IUPHAR \n Subcommittee on Hydroxycarboxylic acid receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21454438?dopt=AbstractPlus ]) respond to organic acids, including the endogenous hydroxy carboxylic acids 3‐hydroxy butyric acid and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2932 , as well as the lipid lowering agents  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1588  (niacin),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1596  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1595  [ http://www.ncbi.nlm.nih.gov/pubmed/12646212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12563315?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12522134?dopt=AbstractPlus ]. These receptors were provisionally described as nicotinic acid receptors, although nicotinic acid shows submicromolar potency at HCA 2  receptors only and is unlikely to be the natural ligand [ http://www.ncbi.nlm.nih.gov/pubmed/12563315?dopt=AbstractPlus ,  https://www.ncbi.nlm.nih.gov/pubmed/12522134?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=311 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=312 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=313 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4532 ,  http://www.uniprot.org/uniprot/Q9BXC0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24827 ,  http://www.uniprot.org/uniprot/Q8TDS4 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16824 ,  http://www.uniprot.org/uniprot/P49019 \n Potency order of endogenous ligands – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1593  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1059 \n – Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2932  [ http://www.ncbi.nlm.nih.gov/pubmed/20374963?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18952058?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19047060?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1593  [ http://www.ncbi.nlm.nih.gov/pubmed/15929991?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1059 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2933  [ http://www.ncbi.nlm.nih.gov/pubmed/19561068?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8467  [ http://www.ncbi.nlm.nih.gov/pubmed/24486398?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5783  [ http://www.ncbi.nlm.nih.gov/pubmed/22434674?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8469  [ http://www.ncbi.nlm.nih.gov/pubmed/24900372?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8470  [ http://www.ncbi.nlm.nih.gov/pubmed/25773497?dopt=AbstractPlus ] – Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5788  [ http://www.ncbi.nlm.nih.gov/pubmed/20184326?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5785  [ http://www.ncbi.nlm.nih.gov/pubmed/22435740?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1588  [ http://www.ncbi.nlm.nih.gov/pubmed/12646212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12563315?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12522134?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1596  [ https://www.ncbi.nlm.nih.gov/pubmed/12646212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12522134?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5786  [ http://www.ncbi.nlm.nih.gov/pubmed/18722346?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5800  [ http://www.ncbi.nlm.nih.gov/pubmed/19524438?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1597  [ http://www.ncbi.nlm.nih.gov/pubmed/16480258?dopt=AbstractPlus ] Labelled ligands – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1594  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12646212?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12563315?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12522134?dopt=AbstractPlus ] –\nFurther closely‐related GPCRs include the  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=35  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24884 ,  http://www.uniprot.org/uniprot/Q8TDS5 )and  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4486  ( http://www.uniprot.org/uniprot/O00270 ). Lactate activates HCA 1  on adipocytes in an autocrine manner. It inhibits lipolysis and thereby promotes anabolic effects. HCA 2  and HCA 3  regulate adipocyte lipolysis and immune functions under conditions of increased FFA formation through lipolysis (e.g., during fasting). HCA 2  agonists acting mainly through the receptor on immune cells exert antiatherogenic and anti‐inflammatory effects. HCA 2  is also a receptor for butyrate and mediates some of the beneficial effects of short‐chain fatty acids produced by gut microbiota. HCA 3  has been shown to be activated by aromatic D‐amino acids.\nBoatman PD  et al . (2008) Nicotinic acid receptor agonists.  J. Med. Chem. \n 51 : 7653‐62  https://www.ncbi.nlm.nih.gov/pubmed/18983141?dopt=AbstractPlus\nGraff EC  et al . (2016) Anti‐inflammatory effects of the hydroxycarboxylic acid receptor 2.  Metab. Clin. Exp. \n 65 : 102‐13  https://www.ncbi.nlm.nih.gov/pubmed/26773933?dopt=AbstractPlus\nKamanna VS  et al . (2013) Recent advances in niacin and lipid metabolism.  Curr. Opin. Lipidol. \n 24 : 239‐45 [ https://www.ncbi.nlm.nih.gov/pubmed/23619367?dopt=AbstractPlus ]\nOffermanns S. (2017) Hydroxy‐Carboxylic Acid Receptor Actions in Metabolism.  Trends Endocrinol. \n Metab. \n 28 : 227‐236  https://www.ncbi.nlm.nih.gov/pubmed/28087125?dopt=AbstractPlus\nOffermanns S  et al . (2011) International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy‐carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B).  Pharmacol. Rev. \n 63 : 269‐90  https://www.ncbi.nlm.nih.gov/pubmed/21454438?dopt=AbstractPlus\nOffermanns S  et al . (2015) Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation.  Trends Mol Med \n 21 : 245‐55  https://www.ncbi.nlm.nih.gov/pubmed/25766751?dopt=AbstractPlus\n\nThe kisspeptin receptor ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the kisspeptin receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/21079036?dopt=AbstractPlus ]), like neuropeptide FF (NPFF), prolactin‐releasing peptide (PrP) and QRFP receptors (provisional nomenclature) responds to endogenous peptides with an arginine‐phenylalanine amide (RFamide) motif.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1288  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ,  http://www.uniprot.org/uniprot/Q15726 ) (KP54, originally named metastin),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1284  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ,  http://www.uniprot.org/uniprot/Q15726 ) (KP13) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1283  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ) (KP10) are biologically‐active peptides cleaved from the  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341  ( http://www.uniprot.org/uniprot/Q15726 ) gene product. Kisspeptins have roles in, for example, cancer metastasis, fertility/puberty regula tion and glucose homeostasis.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=266 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4510 ,  http://www.uniprot.org/uniprot/Q969F8 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1283  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11457843?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11385580?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1288  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ,  http://www.uniprot.org/uniprot/Q15726 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11457843?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11385580?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1285  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ,  http://www.uniprot.org/uniprot/Q15726 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11457843?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1284  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6341 ,  http://www.uniprot.org/uniprot/Q15726 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11457843?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4014  [ http://www.ncbi.nlm.nih.gov/pubmed/18302161?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4015  [ http://www.ncbi.nlm.nih.gov/pubmed/19934405?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10222  [ http://www.ncbi.nlm.nih.gov/pubmed/27589480?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4012  [ http://www.ncbi.nlm.nih.gov/pubmed/19321788?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1280  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11385580?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3792 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17023533?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1281 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11457843?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4013 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17023533?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10223  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/30044673?dopt=AbstractPlus ]\n2‐acylamino‐4,6‐diphenylpyridine derivatives have been described and are the first small molecule kisspeptin receptor antagonists reported with potential for treatment of sex‐hormone dependent diseases such as prostate cancer and endometriosis [ http://www.ncbi.nlm.nih.gov/pubmed/20580563?dopt=AbstractPlus ] .\nHarter CJL  et al . (2018) The role of kisspeptin neurons in reproduction and metabolism.  J. Endocrinol. \n 238 : R173‐R183  https://www.ncbi.nlm.nih.gov/pubmed/30042117?dopt=AbstractPlus\nKanda S  et al . (2013) Structure, synthesis, and phylogeny of kisspeptin and its receptor.  Adv. Exp. Med. Biol. \n 784 : 9‐26  https://www.ncbi.nlm.nih.gov/pubmed/23550000?dopt=AbstractPlus\nKirby HR  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function.  Pharmacol. Rev. \n 62 : 565‐78  https://www.ncbi.nlm.nih.gov/pubmed/21079036?dopt=AbstractPlus\nOakley AE  et al . (2009) Kisspeptin signaling in the brain.  Endocr. Rev. \n 30 : 713‐43  https://www.ncbi.nlm.nih.gov/pubmed/19770291?dopt=AbstractPlus\nPasquier J  et al . (2014) Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors.  J. Mol. Endocrinol. \n 52 : T101‐17  https://www.ncbi.nlm.nih.gov/pubmed/24577719?dopt=AbstractPlus\n\nThe leukotriene receptors ( nomenclature as agreed by the  NC‐IUPHAR  subcommittee on Leukotriene Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/21771892?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus ]) are activated by the endogenous ligands leukotrienes (LT), synthesized from lipoxygenase metabolism of arachidonic acid. The human BLT 1  receptor is the high affinity LTB 4  receptor whereas the BLT 2  receptor in addition to being a low‐affinity LTB 4  receptor also binds several other lipoxygenase‐products, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3404 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2481 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3401 , and the thromboxane synthase product  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6159 . The BLT receptors mediate chemotaxis and immunomodulation in several leukocyte populations and are in addition expressed on non‐myeloid cells, such as vascular smooth muscle and endothelial cells. In addition to BLT receptors, LTB 4  has been reported to bind to the peroxisome proliferator activated receptor (PPAR) α [ http://www.ncbi.nlm.nih.gov/pubmed/9890897?dopt=AbstractPlus ] and the vanilloid TRPV1 ligand‐gated nonselective cation channel [ http://www.ncbi.nlm.nih.gov/pubmed/16207832?dopt=AbstractPlus ]. The receptors for the cysteinyl‐leukotrienes ( i.e. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3352 ) aretermed CysLT 1  and CysLT 2  and exhibit distinct expression patterns in human tissues, mediating for example smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation. There is also evidence in the literature for additional CysLT receptor subtypes, derived from functional in vitro studies, radioligand binding and in mice lacking both CysLT 1  and CysLT 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus ]. Cysteinyl‐leukotrienes have also been suggested to signal through the P2Y 12  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/20702811?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16185654?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19822647?dopt=AbstractPlus ], GPR17 [ http://www.ncbi.nlm.nih.gov/pubmed/16990797?dopt=AbstractPlus ] and GPR99 [ http://www.ncbi.nlm.nih.gov/pubmed/23504326?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=267 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=268 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=269 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=270 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=271 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=223 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6713 ,  http://www.uniprot.org/uniprot/Q15722 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19260 ,  http://www.uniprot.org/uniprot/Q9NPC1 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17451 ,  http://www.uniprot.org/uniprot/Q9Y271 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18274 ,  http://www.uniprot.org/uniprot/Q9NS75 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24884 ,  http://www.uniprot.org/uniprot/Q8TDS5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3827 ,  http://www.uniprot.org/uniprot/P25090 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2487  > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3399  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3405  [ http://www.ncbi.nlm.nih.gov/pubmed/11278893?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6159  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2487  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3404  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2481  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3401  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3405  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3399  [ http://www.ncbi.nlm.nih.gov/pubmed/18378794?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11278893?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3352  [ http://www.ncbi.nlm.nih.gov/pubmed/10391245?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10462554?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354  ≥  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3352  [ http://www.ncbi.nlm.nih.gov/pubmed/10851239?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11093801?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10913337?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3391 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3392 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6164  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6167  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2483  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3390  [ http://www.ncbi.nlm.nih.gov/pubmed/19450703?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12065583?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12606753?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9829988?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18292294?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1326548?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7797484?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3933  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3383  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3354  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3353  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3402  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1022  [ http://www.ncbi.nlm.nih.gov/pubmed/10393980?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8006586?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8527441?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11141472?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9151906?dopt=AbstractPlus ] Endogenous agonists – – – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034  [ http://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3934  [ https://www.ncbi.nlm.nih.gov/pubmed/20080636?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6239  [ http://www.ncbi.nlm.nih.gov/pubmed/22449948?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3933 \n Selective agonists – – – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3383  [ http://www.ncbi.nlm.nih.gov/pubmed/15056011?dopt=AbstractPlus ] Endogenous antagonists – – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6171  (pIC 50  6.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9920859?dopt=AbstractPlus ] – Antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3634  (p K \n i  7.1–8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9504401?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11996896?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3334  (p K i 7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9547367?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3634  (p A \n 2  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/25839425?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3334  (p A \n 2  6.2) [ http://www.ncbi.nlm.nih.gov/pubmed/25839425?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6154  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/11259574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17170051?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3368  (pIC 50  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/7714764?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3325  (p K \n i  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10513580?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3351  (pIC 50  6–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/1316967?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11278893?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3358  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/2170649?dopt=AbstractPlus ] – Guinea pig,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3322  (zafirlukast is only about 100‐fold selective for CysLT 1 ) (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9504401?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11996896?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3340  (p K i 8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/11996896?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10346  (pIC 50  8) [ http://www.ncbi.nlm.nih.gov/pubmed/10391245?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6196  (p A \n 2  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/21753081?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6196  (p A \n 2  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21753081?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6197  (pIC 50  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/20423349?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1040  (pIC 50  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/15210823?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1030  (pIC 50  4.3–6) [ http://www.ncbi.nlm.nih.gov/pubmed/6280748?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17687636?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10882119?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3413  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9177352?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3415  (Antagonist) (p K \n d  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/1320692?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3413  (p K \n d  7.6–9.7) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3412  (Agonist),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3414  (Antagonist) (p K \n d  10.6) [ http://www.ncbi.nlm.nih.gov/pubmed/1329767?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3412  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10851239?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3416  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9829988?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3411  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8006586?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1322894?dopt=AbstractPlus ]\nThe FPR2/ALX receptor ( nomenclatureas agreed by the  NC‐IUPHAR  subcommittee on Leukotriene and Lipoxin Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus ]) is activated by the endogenous lipidderived, anti‐inflammatory ligands lipoxin A 4  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1034 ) and 15‐epiLXA 4  ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3933 , ATL). The FPR2/ALX receptor also interacts with endogenous peptide and protein ligands, such as MHC binding peptide [ http://www.ncbi.nlm.nih.gov/pubmed/10748237?dopt=AbstractPlus ] as well as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1031  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:533 ,  http://www.uniprot.org/uniprot/P04083 ) (ANXA1) and its  N ‐terminal peptides [ http://www.ncbi.nlm.nih.gov/pubmed/24108355?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12368905?dopt=AbstractPlus ]. In addition, a soluble hydrolytic product of protease action on the urokinase‐type plasminogen activator receptor has been reported to activate the FPR2/ALX receptor [ http://www.ncbi.nlm.nih.gov/pubmed/11818541?dopt=AbstractPlus ]. Furthermore, FPR2/ALX has been suggested to act as a receptor mediating the proinflammatory actions of the acute‐phase reactant, serum amyloid A [ http://www.ncbi.nlm.nih.gov/pubmed/15171815?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9892621?dopt=AbstractPlus ]. The agonist activity of the lipid mediators described has been questioned [ http://www.ncbi.nlm.nih.gov/pubmed/23643932?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23607720?dopt=AbstractPlus ], which may derive from batchto‐batch differences, partial agonism or biased agonism. Results from Cooray  et al.  (2013) [ http://www.ncbi.nlm.nih.gov/pubmed/24108355?dopt=AbstractPlus ] have addressed this issue and the role of homodimers and heterodimers in intracellular signaling. A receptor selective for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5216  has been suggested from functional studies [ http://www.ncbi.nlm.nih.gov/pubmed/12794159?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8551217?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8757340?dopt=AbstractPlus ]. Note that the data for FPR2/ALX are also reproduced on the  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=23 .\nOxoeicosanoid receptors (OXE,  nomenclature agreed by the \n NC‐IUPHAR subcommittee on Oxoeicosanoid Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/15001665?dopt=AbstractPlus ] ) are activated by endogenous chemotactic eicosanoid ligands oxidised at the C‐5 position, with  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3391  the most potent agonist identified for this receptor. Initial characterization of the heterologously expressed OXE receptor suggested that polyunsaturated fatty acids, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1051  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3362 , acted as receptor antagonists [ http://www.ncbi.nlm.nih.gov/pubmed/12065583?dopt=AbstractPlus ].\nBrink C  et al . (2004) International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor.  Pharmacol. Rev. \n 56 : 149‐157  https://www.ncbi.nlm.nih.gov/pubmed/15001665?dopt=AbstractPlus\nBrink C  et al . (2003) International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors.  Pharmacol. Rev. \n 55 : 195‐227  https://www.ncbi.nlm.nih.gov/pubmed/12615958?dopt=AbstractPlus\nBäck M  et al . (2011) International Union of Basic and Clinical Pharmacology. LXXXIV: leukotriene receptor nomenclature, distribution, and pathophysiological functions.  Pharmacol. Rev. \n 63 : 539‐84  https://www.ncbi.nlm.nih.gov/pubmed/21771892?dopt=AbstractPlus\nBäck M  et al . (2014) Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7.  Br. J. Pharmacol. \n 171 : 3551‐74  https://www.ncbi.nlm.nih.gov/pubmed/24588652?dopt=AbstractPlus\nLaidlaw TM  et al . (2012) Cysteinyl leukotriene receptors, old and new; implications for asthma.  Clin. Exp. Allergy \n 42 : 1313‐20  https://www.ncbi.nlm.nih.gov/pubmed/22925317?dopt=AbstractPlus\n\nLysophosphatidic acid (LPA) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Lysophospholipid (LPA) receptors Lysophospholipid Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24602016?dopt=AbstractPlus ]) are activated by the endogenous phospholipid  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2906 . The first receptor, LPA 1 , was identified as  ventricular zone gene‐1  ( vzg‐1 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8922387?dopt=AbstractPlus ], leading to deorphanisation of members of the endothelial differentiation gene ( edg ) family as other LPA receptors along with sphingosine 1phosphate (S1P) receptors. Additional LPA receptor GPCRs were later identified. Gene names have been codified as  LPAR1 ,  etc . to reflect the receptor function of proteins. The crystal structure of LPA 1  was solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery  via  autotaxin [ http://www.ncbi.nlm.nih.gov/pubmed/26091040?dopt=AbstractPlus ]. These studies have also implicated cross‐talk with endocannabinoids  via  phosphorylated intermediates that can also activate these receptors. The identified receptors can account for most, although not all, LPA‐induced phenomena in the literature, indicating that a majority of LPA‐dependent phenomena are receptor‐mediated. Binding affinities of unlabeled, natural LPA and AEApto LPA 1  weremeasured using backscattering interferometry (pK d  = 9) [ http://www.ncbi.nlm.nih.gov/pubmed/30463988?dopt=AbstractPlus ]. Binding affinities were 77‐fold lower than than values obtained using radioactivity [ http://www.ncbi.nlm.nih.gov/pubmed/19386608?dopt=AbstractPlus ]. Targeted deletion of LPA receptors has clarified signalling pathways and identified physiological and pathophysiological roles. Independent validation by multiple groups has been reported in the peer‐reviewed literature for all six LPA receptors described in the tables, including further validation using a distinct read‐out  via  a novel TGFα “shedding” assay [ http://www.ncbi.nlm.nih.gov/pubmed/22983457?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2906  has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [ http://www.ncbi.nlm.nih.gov/pubmed/22101604?dopt=AbstractPlus ] and TRPA1 [ http://www.ncbi.nlm.nih.gov/pubmed/28176353?dopt=AbstractPlus ]. LPA was originally proposed to be a ligand for GPCR35, but data show that in fact it is a receptor for  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6479  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19232 ,  http://www.uniprot.org/uniprot/Q6UXB2 ) [ http://www.ncbi.nlm.nih.gov/pubmed/25411203?dopt=AbstractPlus ]. All of these proposed non‐GPCR receptor identities require confirmation and are not currently recognized as  bona fide  LPA receptors.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=272 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=273 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=274 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=94 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=124 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=163 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3166 ,  http://www.uniprot.org/uniprot/Q92633 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3168 ,  http://www.uniprot.org/uniprot/Q9HBW0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14298 ,  http://www.uniprot.org/uniprot/Q9UBY5 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4478 ,  http://www.uniprot.org/uniprot/Q99677 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13307 ,  http://www.uniprot.org/uniprot/Q9H1C0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15520 ,  http://www.uniprot.org/uniprot/P43657 \n Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4031  [ http://www.ncbi.nlm.nih.gov/pubmed/12695531?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4030  [ https://www.ncbi.nlm.nih.gov/pubmed/12695531?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6580  [ http://www.ncbi.nlm.nih.gov/pubmed/22968304?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2912  [ http://www.ncbi.nlm.nih.gov/pubmed/12554733?dopt=AbstractPlus ] – – – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2907  (pIC 50  6.6–6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/14500756?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2909  (p K \n i  5.2–6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/11723223?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5450  [ http://www.ncbi.nlm.nih.gov/pubmed/15125924?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2909  (p K \n i  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/11723223?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5450  [ http://www.ncbi.nlm.nih.gov/pubmed/15125924?dopt=AbstractPlus ] – – – Sub/family‐selective antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2907  (p K \n i  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/14500756?dopt=AbstractPlus ] – – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9498  (pIC 50  8.9),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2905  (pIC 50  6.7–7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/21159750?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9499  (pIC 50  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/27774128?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6988  (pIC 50  6–6.1) [ http://www.ncbi.nlm.nih.gov/pubmed/21159750?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2916  (p K \n i  5.5–7) [ http://www.ncbi.nlm.nih.gov/pubmed/11562440?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14500756?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10230  (pIC 50  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/28859883?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9500  (pIC 50  6.1) [ http://www.ncbi.nlm.nih.gov/pubmed/22801643?dopt=AbstractPlus ] –\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2907  [ http://www.ncbi.nlm.nih.gov/pubmed/14500756?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2909  [ http://www.ncbi.nlm.nih.gov/pubmed/11723223?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5450  [ http://www.ncbi.nlm.nih.gov/pubmed/15125924?dopt=AbstractPlus ] have dual antagonist activity at LPA 1  and LPA 3  receptors. There is growing evidence for  in vivo  efficacy of these chemical antagonists in several disorders, including fetal hydrocephalus [ http://www.ncbi.nlm.nih.gov/pubmed/21900594?dopt=AbstractPlus ], fetal hypoxia [ http://www.ncbi.nlm.nih.gov/pubmed/21878565?dopt=AbstractPlus ], lung fibrosis [ http://www.ncbi.nlm.nih.gov/pubmed/25959255?dopt=AbstractPlus ], systemic sclerosis [ http://www.ncbi.nlm.nih.gov/pubmed/25959255?dopt=AbstractPlus ] and atherosclerosis progression [ http://www.ncbi.nlm.nih.gov/pubmed/27883026?dopt=AbstractPlus ]. The LPA 2  selective agonist,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6580 , also shows efficacy in an animal model of multiple sclerosis [ http://www.ncbi.nlm.nih.gov/pubmed/28578681?dopt=AbstractPlus ]. The LPA5 selective antagonist,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10230 , is effective in pain models [ http://www.ncbi.nlm.nih.gov/pubmed/29208511?dopt=AbstractPlus ].\nChun J  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature.  Pharmacol. Rev. \n 62 : 579‐87  https://www.ncbi.nlm.nih.gov/pubmed/21079037?dopt=AbstractPlus\nKihara Y  et al . (2014) Lysophospholipid receptor nomenclature review: IUPHAR Review 8.  Br. J. Pharmacol. \n 171 : 3575‐94  https://www.ncbi.nlm.nih.gov/pubmed/24602016?dopt=AbstractPlus\nYung YC  et al . (2015) Lysophosphatidic Acid signaling in the nervous system.  Neuron \n 85 : 669‐82  https://www.ncbi.nlm.nih.gov/pubmed/25695267?dopt=AbstractPlus\n\nSphingosine 1‐phosphate (S1P) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Lysophospholipid receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/24602016?dopt=AbstractPlus ]) are activated by the endogenous lipid  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  (S1P). Originally cloned as orphan members of the endothelial differentiation gene ( edg ) family, current gene names have been designated as S1P 1 R through S1P 5 R [ http://www.ncbi.nlm.nih.gov/pubmed/2160972?dopt=AbstractPlus ]. S1PRs, particularly S1P 1 , are expressed throughout all mammalian organ systems. Ligand delivery occurs  via  two known carriers (or “chaperones”): albumin and HDLbound apolipoprotein M (ApoM), the latter of which elicits biased agonist signaling by S1P 1  in multiple cell types [ http://www.ncbi.nlm.nih.gov/pubmed/26053123?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26268607?dopt=AbstractPlus ]. The five S1PRs, two chaperones, and active cellular metabolism have complicated analyses of receptor ligand binding in native systems. Signaling pathways and physiological roles have been characterized through radioligand binding in heterologous expression systems, targeted deletion of the different S1PRs, and most recently, mouse models that report  in vivo  S1P1R activation [ http://www.ncbi.nlm.nih.gov/pubmed/29079828?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24667638?dopt=AbstractPlus ]. A crystal structure of an S1P 1 ‐T4 fusion protein confirmed aspects and binding, specificity, and receptor activation determined previously through biochemical and genetic studies [ http://www.ncbi.nlm.nih.gov/pubmed/30343728?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22344443?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2407  (FTY720), the first drug to target any of the lysophospholipid receptors, binds to four of the five S1PRs, and was the first oral therapy for multiple sclerosis [ http://www.ncbi.nlm.nih.gov/pubmed/30625282?dopt=AbstractPlus ]. The mechanisms of action of fingolimod and other S1PR modulating drugs in development include binding S1PRs in multiple organ systems,  e.g. , immune and nervous systems, although the precise nature of their receptor interactions requires clarification [ http://www.ncbi.nlm.nih.gov/pubmed/21520239?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23518370?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30255127?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25831442?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=275 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=276 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=277 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=278 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=279 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3165 ,  http://www.uniprot.org/uniprot/P21453 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3169 ,  http://www.uniprot.org/uniprot/O95136 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3167 ,  http://www.uniprot.org/uniprot/Q99500 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3170 ,  http://www.uniprot.org/uniprot/O95977 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14299 ,  http://www.uniprot.org/uniprot/Q9H228 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2921  [ http://www.ncbi.nlm.nih.gov/pubmed/10383399?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9765227?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2921  [ http://www.ncbi.nlm.nih.gov/pubmed/10383399?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9765227?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2921  [ http://www.ncbi.nlm.nih.gov/pubmed/9765227?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2921  [ http://www.ncbi.nlm.nih.gov/pubmed/10753843?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=911  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2921  [ http://www.ncbi.nlm.nih.gov/pubmed/10799507?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14747617?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9289  [ http://www.ncbi.nlm.nih.gov/pubmed/29735753?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24900670?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9331  [ http://www.ncbi.nlm.nih.gov/pubmed/25516790?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14747617?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14747617?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14747617?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17114004?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14732717?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25347187?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9331  [ http://www.ncbi.nlm.nih.gov/pubmed/12110609?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25516790?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14747617?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17114004?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9289  [ http://www.ncbi.nlm.nih.gov/pubmed/9735753?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22646698?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24125884?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9331  [ http://www.ncbi.nlm.nih.gov/pubmed/25516790?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10309  [ http://www.ncbi.nlm.nih.gov/pubmed/21445057?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9320  [ http://www.ncbi.nlm.nih.gov/pubmed/20446681?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9824  [ http://www.ncbi.nlm.nih.gov/pubmed/29226621?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2928  [ http://www.ncbi.nlm.nih.gov/pubmed/18708635?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2926  [ http://www.ncbi.nlm.nih.gov/pubmed/14732717?dopt=AbstractPlus ] – Mouse – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9494  [ http://www.ncbi.nlm.nih.gov/pubmed/22971058?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10311  [ http://www.ncbi.nlm.nih.gov/pubmed/21982495?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9496  [ http://www.ncbi.nlm.nih.gov/pubmed/29688337?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26509640?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3324  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15590668?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6992  (p K \n i  7.6–7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/21632869?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2930  (pIC 50  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/17113298?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2930  (p K \n i  6.5) [ http://www.ncbi.nlm.nih.gov/pubmed/17113298?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3324  (p K \n i  5.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15590668?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6997  (pIC 50  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/22999882?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2931  (p K \n i  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16829954?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2917  (pIC 50  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12445827?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10310  (p K \n i  7) [ http://www.ncbi.nlm.nih.gov/pubmed/20097776?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10312  (pIC 50  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/23913862?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21570287?dopt=AbstractPlus ] –\nThe FDA‐approved immunomodulator  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2407  (FTY720) is phosphorylated  in vivo  [ http://www.ncbi.nlm.nih.gov/pubmed/16078855?dopt=AbstractPlus ] to generatean agonist with activity at S1P 1 , S1P 3 , S1P 4  and S1P 5  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/11967257?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11923495?dopt=AbstractPlus ]. Many of the physiological consequences of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2924  administration, as well as those of other currently described S1P 1  agonists, may involve functional antagonism  via  ubiquitination and subsequent degradation of S1P 1  [ http://www.ncbi.nlm.nih.gov/pubmed/17237497?dopt=AbstractPlus ]. Additionally, receptor specificities of the different compounds may depend on the functional assay system utilized and from which species the receptor sequence originated.\nChew WS  et al . (2016) To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.  Pharmacol. Res. \n 113 : 521‐532  https://www.ncbi.nlm.nih.gov/pubmed/27663260?dopt=AbstractPlus\nChun J  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature.  Pharmacol. Rev. \n 62 : 579‐87  https://www.ncbi.nlm.nih.gov/pubmed/21079037?dopt=AbstractPlus\nCyster JG  et al . (2012) Sphingosine‐1‐phosphate and lymphocyte egress from lymphoid organs.  Annu. Rev. Immunol. \n 30 : 69‐94  https://www.ncbi.nlm.nih.gov/pubmed/22149932?dopt=AbstractPlus\nPyne NJ  et al . (2017) Sphingosine 1‐Phosphate Receptor 1 Signaling in Mammalian Cells.  Molecules \n 22 :  https://www.ncbi.nlm.nih.gov/pubmed/28241498?dopt=AbstractPlus\nRosen H  et al . (2013) Sphingosine‐1‐phosphate and its receptors: structure, signaling, and influence.  Annu. Rev. Biochem. \n 82 : 637‐62  https://www.ncbi.nlm.nih.gov/pubmed/23527695?dopt=AbstractPlus\nYanagida K  et al . (2017) Vascular and Immunobiology of the Circulatory Sphingosine 1‐Phosphate Gradient.  Annu. Rev. Physiol. \n 79 : 67‐91  https://www.ncbi.nlm.nih.gov/pubmed/27813829?dopt=AbstractPlus\n\nMelanin‐concentrating hormone (MCH) receptors ( provisional nomenclature as recommended by \n NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by an endogenous nonadecameric cyclic peptide identical in humans and rats (DFDMLRCMLGRVYRPCWQV; mammalian MCH) generated from a precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9109 ,  http://www.uniprot.org/uniprot/P20382 ), which also produces  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5374  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9109 ,  http://www.uniprot.org/uniprot/P20382 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5375  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9109 ,  http://www.uniprot.org/uniprot/P20382 ).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=280 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=281 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4479 ,  http://www.uniprot.org/uniprot/Q99705 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20867 ,  http://www.uniprot.org/uniprot/Q969V1 \n Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4033  (pIC 50  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/16870432?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1313  (p A \n 2  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12118247?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1314  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/11909603?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1305  (pIC 50  7.9–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15677346?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1317 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1317  (Antagonist) (p K \n d  9.2–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11375253?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3844 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3844 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3844 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3844  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9434758?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3827 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3827 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9434758?dopt=AbstractPlus ] –\nThe MCH 2  receptor appears to be a non‐functional pseudogene in rodents [ http://www.ncbi.nlm.nih.gov/pubmed/12036292?dopt=AbstractPlus ].\nChung S  et al . (2011) Recent updates on the melanin‐concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists.  J. Mol. Neurosci. \n 43 : 115‐21 [ https://www.ncbi.nlm.nih.gov/pubmed/20582487?dopt=AbstractPlus ]\nEberle AN  et al . (2010) Cellular models for the study of the pharmacology and signaling of melaninconcentrating hormone receptors.  J. Recept. Signal Transduct. Res. \n 30 : 385‐402 [ https://www.ncbi.nlm.nih.gov/pubmed/21083507?dopt=AbstractPlus ]\nFoord SM  et al . (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57 : 279‐288 [ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nTakase K  et al . (2014) Meta‐analysis of melanin‐concentrating hormone signaling‐deficient mice on behavioral and metabolic phenotypes.  PLoS ONE \n 9 : e99961 [ https://www.ncbi.nlm.nih.gov/pubmed/24924345?dopt=AbstractPlus ]\n\nMelanocortin receptors ( provisional nomenclature as recommended by \n NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by members of the melanocortin family ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ,  http://www.uniprot.org/uniprot/P01189 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ,  http://www.uniprot.org/uniprot/P01189 ) forms;  δ  form is not found in mammals) and adrenocorticotrophin ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633 ,  http://www.uniprot.org/uniprot/P01189 )). Endogenous antagonists include  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3609  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:745 ,  http://www.uniprot.org/uniprot/P42127 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1335  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:330 ,  http://www.uniprot.org/uniprot/O00253 ). ACTH(1‐24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP‐MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=282 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=283 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=284 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=285 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=286 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6929 ,  http://www.uniprot.org/uniprot/Q01726 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6930 ,  http://www.uniprot.org/uniprot/Q01718 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6931 ,  http://www.uniprot.org/uniprot/P41968 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6932 ,  http://www.uniprot.org/uniprot/P32245 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6933 ,  http://www.uniprot.org/uniprot/P33032 \n Potency order of endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ,  http://www.uniprot.org/uniprot/P01189 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320 ,  http://www.uniprot.org/uniprot/P01189 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ,  http://www.uniprot.org/uniprot/P01189 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1320  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3606 ,  http://www.uniprot.org/uniprot/P01189 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3633 ,  http://www.uniprot.org/uniprot/P01189 ) > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1333 ,  http://www.uniprot.org/uniprot/P01189 ) Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6967 \n [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1334 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1334 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1334  [ http://www.ncbi.nlm.nih.gov/pubmed/11150170?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1338  [ http://www.ncbi.nlm.nih.gov/pubmed/12361385?dopt=AbstractPlus ] – Antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6546  (pIC 50  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/17482720?dopt=AbstractPlus ] – – Selective antagonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1339  (pIC 50  10) [ http://www.ncbi.nlm.nih.gov/pubmed/11606131?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1321  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9630346?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15840392?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3767 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3767 ) (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15840392?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3804 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3804  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12604699?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3804 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3804  (Antagonist) (p K \n d  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12604699?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15840392?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7774675?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1326  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15840392?dopt=AbstractPlus ]\nPolymorphisms of the MC 1  receptor have been linked to variations in skin pigmentation. Defects of the MC 2  receptor underlie familial glucocorticoid deficiency. Polymorphisms of the MC4 receptor have been linked to obesity [ http://www.ncbi.nlm.nih.gov/pubmed/9392003?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18779842?dopt=AbstractPlus ].\nCaruso V  et al . (2014) Synaptic changes induced by melanocortin signalling.  Nat. Rev. Neurosci. \n 15 : 98‐110 [ https://www.ncbi.nlm.nih.gov/pubmed/24588018?dopt=AbstractPlus ]\nFoord SM  et al . (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57 : 279‐288 [ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nRenquist BJ  et al . (2011) Physiological roles of the melanocortin MC_3 receptor.  Eur. J. Pharmacol. \n 660 : 13‐20 [ https://www.ncbi.nlm.nih.gov/pubmed/21211527?dopt=AbstractPlus ]\n\nMelatonin receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Melatonin Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/20605968?dopt=AbstractPlus ]) are activated by the endogenous ligands  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=224  and clinically used drugs like  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1356 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=198  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7393 .\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=287 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=288 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7463 ,  http://www.uniprot.org/uniprot/P48039 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7464 ,  http://www.uniprot.org/uniprot/P49286 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=224  [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2991499?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=224  [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2991499?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1356  [ http://www.ncbi.nlm.nih.gov/pubmed/15695169?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=198  [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9618428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7393  [ http://www.ncbi.nlm.nih.gov/pubmed/19054552?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=198  [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9618428?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1356  [ http://www.ncbi.nlm.nih.gov/pubmed/15695169?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21182402?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7393  [ http://www.ncbi.nlm.nih.gov/pubmed/19054552?dopt=AbstractPlus ] Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9226  [ http://www.ncbi.nlm.nih.gov/pubmed/26334942?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1350  [ http://www.ncbi.nlm.nih.gov/pubmed/10737738?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10420436?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1364  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ] Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1358  (p K \n i  8.8–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9737724?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1359  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10737738?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10420436?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3366  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/9840420?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7770 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7770  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/23698757?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1344 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1344  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1357 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1357  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10696085?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7770 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7770  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/23698757?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1344 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1344  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12764576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9089668?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7771 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7771  (Agonist, Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/23698757?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1357 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1357  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10696085?dopt=AbstractPlus ]\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=224 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1343 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=198 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1349 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1351  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1356  [ http://www.ncbi.nlm.nih.gov/pubmed/15695169?dopt=AbstractPlus ] are nonselective agonists for MT 1  and MT 2  receptors. (‐)‐AMMTC displays an ˜400‐fold greater agonist potency than (+)‐AMMTC at rat MT 1  receptors (see  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3385  for structure) [ http://www.ncbi.nlm.nih.gov/pubmed/10433507?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1363  is an MT 1 /MT 2  non‐selective competitive melatonin receptor antagonist with about 15‐25 fold selectivity for the MT 2  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/9737724?dopt=AbstractPlus ]. MT 1 /MT 2  heterodimers present differentpharmacological profiles from MT 1  and MT 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/15266022?dopt=AbstractPlus ]. The  MT3  binding site of hamster brain and peripheral tissues such as kidney and testis, also termed the ML 2  receptor, binds selectively  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5396 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5396  [ http://www.ncbi.nlm.nih.gov/pubmed/8773460?dopt=AbstractPlus ]. Pharmacological investigations of  MT 3  binding sites have primarily been conducted in hamster tissues. At this site, The endogenous ligand  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5451  [ http://www.ncbi.nlm.nih.gov/pubmed/8246675?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9283717?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9283717?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7798906?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3393  [ http://www.ncbi.nlm.nih.gov/pubmed/7798906?dopt=AbstractPlus ] appear to function as agonists, while  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=503  [ http://www.ncbi.nlm.nih.gov/pubmed/9283717?dopt=AbstractPlus ] functions as an antagonist. The  MT 3  binding site of hamster kidney was also identified as the hamster homologue of human quinone reductase 2 ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7856 ,  http://www.uniprot.org/uniprot/P16083  [ http://www.ncbi.nlm.nih.gov/pubmed/10913150?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11331072?dopt=AbstractPlus ]). The  MT 3  binding site activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3393  in eye ciliary body is positively coupled to adenylyl cyclase and regulates chloride secretion [ http://www.ncbi.nlm.nih.gov/pubmed/25344385?dopt=AbstractPlus ].  Xenopus  melanophores and chick brain express a distinct receptor (x420,  P49219 ; c346,  P49288 , initially termed Mel 1C ) coupled to the G i/o  family of G proteins, for which GPR50 has recently been suggested to be a mammalian counterpart [ http://www.ncbi.nlm.nih.gov/pubmed/18400093?dopt=AbstractPlus ] although  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=224  does not bind to GPR50 receptors. Several variants of the  MTNR1B  gene have been associated with increased type 2 diabetes risk [ http://www.ncbi.nlm.nih.gov/pubmed/30531911?dopt=AbstractPlus ].\nCecon E  et al . (2018) Melatonin receptors: molecular pharmacology and signalling in the context of system bias.  Br. J. Pharmacol. \n 175 : 3263‐3280 [ https://www.ncbi.nlm.nih.gov/pubmed/28707298?dopt=AbstractPlus ]\nDubocovich ML  et al . (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein‐coupled melatonin receptors.  Pharmacol. Rev. \n 62 : 343‐80 [ https://www.ncbi.nlm.nih.gov/pubmed/20605968?dopt=AbstractPlus ]\nJockers R  et al . (2016) Update on melatonin receptors: IUPHAR Review 20.  Br. J. Pharmacol. \n 173 : 2702‐25 [ https://www.ncbi.nlm.nih.gov/pubmed/27314810?dopt=AbstractPlus ]\nKaramitri A  et al . (2019) Melatonin in type 2 diabetes mellitus and obesity.  Nat Rev Endocrinol \n 15 : 105‐125 [ https://www.ncbi.nlm.nih.gov/pubmed/30531911?dopt=AbstractPlus ]\nLiu J  et al . (2016) MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.  Annu. Rev. Pharmacol. Toxicol. \n 56 : 361‐83 [ https://www.ncbi.nlm.nih.gov/pubmed/26514204?dopt=AbstractPlus ]\nZlotos DP  et al . (2014) MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential.  J. Med. Chem. \n 57 : 3161‐85 [ https://www.ncbi.nlm.nih.gov/pubmed/24228714?dopt=AbstractPlus ]\n\nMetabotropic glutamate (mGlu) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Metabotropic Glutamate Receptors[1899] ) area family of G protein‐coupled receptors activated by the neurotransmitter glutamate. The mGlu family is composed of eight members (named mGlu1 to mGlu8) which are divided in three groups based on similarities of agonist pharmacology, primary sequence and G protein coupling to effector: Group‐I (mGlu 1  and mGlu 5 ), Group‐II (mGlu 2  and mGlu 3 ) and Group‐III (mGlu 4 , mGlu 6 , mGlu 7  and mGlu 8 ) (see Further reading).\nStructurally, mGlu are composed of three juxtaposed domains: a core G protein‐activating seven‐transmembrane domain (TM), common to all GPCRs, is linked via a rigid cysteine‐rich domain (CRD) to the Venus Flytrap domain (VFTD), a large bi‐lobed extracellular domain where glutamate binds. The structures of the VFTD of mGlu 1 , mGlu 2 , mGlu 3 , mGlu5 and mGlu7 have been solved [ http://www.ncbi.nlm.nih.gov/pubmed/11069170?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25602126?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17360426?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11867751?dopt=AbstractPlus ]. The structure of the 7 transmembrane (TM) domains of both mGlu1 and mGlu5 have been solved, and confirm a general helical organization similar to that of other GPCRs, although the helices appear more compacted [ http://www.ncbi.nlm.nih.gov/pubmed/29455526?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25042998?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24603153?dopt=AbstractPlus ]. mGlu form constitutive dimers crosslinked by a disulfide bridge. Recent studies revealed the possible formation of heterodimers between either group‐I receptors, or within and between group‐II and ‐III receptors [ http://www.ncbi.nlm.nih.gov/pubmed/20826542?dopt=AbstractPlus ]. Although well characterized in transfected cells, co‐localization and specific pharmacological properties also suggest the existence of such heterodimers in the brain [ http://www.ncbi.nlm.nih.gov/pubmed/28661401?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24381270?dopt=AbstractPlus ].\nThe endogenous ligands of mGlu are  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1411 , N‐acetylaspartylglutamate ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1405 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5447 . Group‐I mGlu receptors may be activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1367  and ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1366 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1366  [ http://www.ncbi.nlm.nih.gov/pubmed/8532171?dopt=AbstractPlus ] and antagonized by ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5448  [ http://www.ncbi.nlm.nih.gov/pubmed/15996690?dopt=AbstractPlus ]. Group‐II mGlu receptors may be activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3349  [ http://www.ncbi.nlm.nih.gov/pubmed/10090786?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1394 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1393  [ http://www.ncbi.nlm.nih.gov/pubmed/9144636?dopt=AbstractPlus \n http://www.ncbi.nlm.nih.gov/pubmed/9473604?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1377  and ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1392 , http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1392 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1392  [ http://www.ncbi.nlm.nih.gov/pubmed/9076745?dopt=AbstractPlus , and antagonised by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1400  [ http://www.ncbi.nlm.nih.gov/pubmed/9121605?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3350  [ http://www.ncbi.nlm.nih.gov/pubmed/9871538?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8632404?dopt=AbstractPlus ]. Group‐III mGlu receptors may be activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1410  and ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1406 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1406  [ http://www.ncbi.nlm.nih.gov/pubmed/10336568?dopt=AbstractPlus ]. An example of an antagonist selective for mGlu receptors is  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1378 , which blocks mGlu 2  and mGlu 3  at low nanomolar concentrations, mGlu 8  at high nanomolar concentrations, and mGlu4, mGlu5, and mGlu7 in the micromolar range [ http://www.ncbi.nlm.nih.gov/pubmed/9680254?dopt=AbstractPlus ]. In addition to orthosteric ligands that directly interact with the glutamate recognition site, allosteric modulators that bind within the TM domain have been described. Negative allosteric modulators are listed separately. The positive allosteric modulators most often act as ‘potentiators’ of an orthosteric agonist response, without significantly activating the receptor in the absence of agonist.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=289 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=290 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=291 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=292 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=293 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4593 ,  http://www.uniprot.org/uniprot/Q13255 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4594 ,  http://www.uniprot.org/uniprot/Q14416 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4595 ,  http://www.uniprot.org/uniprot/Q14832 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4596 ,  http://www.uniprot.org/uniprot/Q14833 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4597 ,  http://www.uniprot.org/uniprot/P41594 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1405  [ http://www.ncbi.nlm.nih.gov/pubmed/10884552?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] Agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1410  [ http://www.ncbi.nlm.nih.gov/pubmed/9473604?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1411 ] – Selective agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6706  [ http://www.ncbi.nlm.nih.gov/pubmed/22223752?dopt=AbstractPlus ] ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3421  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10428410?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1417  [ http://www.ncbi.nlm.nih.gov/pubmed/11080213?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1379  (pIC 50  5.1) [400] – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1414  (p K \n i  4.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10187777?dopt=AbstractPlus ] – Rat – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3396  (pIC 50  5.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12015200?dopt=AbstractPlus ] – Rat, ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3421  (pIC 50  4.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10428410?dopt=AbstractPlus ] – Rat, ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3419  (pIC 50  4.2) [ http://www.ncbi.nlm.nih.gov/pubmed/11249114?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1376  (p A \n 2  4.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9152378?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3335  (pIC 50  5.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8667369?dopt=AbstractPlus ] – Rat – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3388  (pIC 50  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15686941?dopt=AbstractPlus ] Allosteric modulators – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3372  (Positive) (pEC 50  7) [ http://www.ncbi.nlm.nih.gov/pubmed/15717213?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1402  (Positive) (pIC 50  5.8) [ http://www.ncbi.nlm.nih.gov/pubmed/15149652?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12852748?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12852748?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14500736?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6221  (Negative) (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/17416742?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10237  (Negative) (pIC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/26335039?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1432  (Positive) (pEC 50  6.3–6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12684257?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1426  (Positive) (pEC 50  6.3–6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/12684257?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1416  (Positive) (pEC 50  4.5) [ http://www.ncbi.nlm.nih.gov/pubmed/14573382?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8543  (Negative) (pIC 50  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/25173999?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1422  (Positive) (pEC 50  7.6–8) [ http://www.ncbi.nlm.nih.gov/pubmed/15608073?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15537338?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3336  (Negative) (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12473093?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1426  (Negative) (pIC 50  7.4–7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11814808?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10530811?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1434  (Negative) (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/16040814?dopt=AbstractPlus ] Selective allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1381  (Negative) (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11306677?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1385  (Negative) (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15555631?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1386  (Positive) (p K \n i  7.5–7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11606768?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3346  (Negative) (pIC 50  6.9) [ 1270 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1382  (Negative) (pIC 50  5.2–5.8) [ http://www.ncbi.nlm.nih.gov/pubmed/10051528?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3955  (Negative) (pIC 50  7) [ http://www.ncbi.nlm.nih.gov/pubmed/10465539?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3954  (Positive) (pEC 50  7) [ http://www.ncbi.nlm.nih.gov/pubmed/16046122?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8765  (Negative) (pIC 50  6.2) [ http://www.ncbi.nlm.nih.gov/pubmed/23718281?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3956  (Positive) (pEC 50  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/19469556?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3323  (Positive) (pEC 50  6.1) [ http://www.ncbi.nlm.nih.gov/pubmed/18664603?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4059  (Positive) (pEC 50  8) [ http://www.ncbi.nlm.nih.gov/pubmed/16722652?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=294 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=295 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=296 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4598 ,  http://www.uniprot.org/uniprot/O15303 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4599 ,  http://www.uniprot.org/uniprot/Q14831 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4600 ,  http://www.uniprot.org/uniprot/O00222 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1411  [ http://www.ncbi.nlm.nih.gov/pubmed/10216218?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9473604?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369  [ http://www.ncbi.nlm.nih.gov/pubmed/10443583?dopt=AbstractPlus ] Agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6706  [ http://www.ncbi.nlm.nih.gov/pubmed/22223752?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1411  [ http://www.ncbi.nlm.nih.gov/pubmed/9473604?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1410 ] ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1407 ) http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1407  [ http://www.ncbi.nlm.nih.gov/pubmed/11166323?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1410  [ http://www.ncbi.nlm.nih.gov/pubmed/10216218?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1436  [ 2158 ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3359  [ http://www.ncbi.nlm.nih.gov/pubmed/8759641?dopt=AbstractPlus ] – – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1414  (pIC 50  3.5) [ http://www.ncbi.nlm.nih.gov/pubmed/12769621?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3326  [ http://www.ncbi.nlm.nih.gov/pubmed/9144637?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1415  (pIC 50  4.3) [ http://www.ncbi.nlm.nih.gov/pubmed/9473604?dopt=AbstractPlus ] Allosteric modulators – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3341  (Negative) (pIC 50  6.1–7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/20026717?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17609420?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6217  (Negative) (pIC 50  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/23257312?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1441  (Positive) (pEC 50  6.5–6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/16339898?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8545  (Negative) (pIC 50  5.6) [ http://www.ncbi.nlm.nih.gov/pubmed/24596089?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10239  (Positive) (p K \n B  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/25225882?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10238  (Positive) (p K \n B  5) [ http://www.ncbi.nlm.nih.gov/pubmed/25225882?dopt=AbstractPlus ]\nThe activity of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1405  as an agonist at mGlu 3  receptors was questioned on the basis of contamination with glutamate [ http://www.ncbi.nlm.nih.gov/pubmed/19389924?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19285517?dopt=AbstractPlus ], but this has been refuted [ http://www.ncbi.nlm.nih.gov/pubmed/21740441?dopt=AbstractPlus ].\nRadioligand binding using a variety of radioligands has been conducted on recombinant receptors (for example, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1391 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1391  [ http://www.ncbi.nlm.nih.gov/pubmed/12695537?dopt=AbstractPlus ] and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5392 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5392  [ http://www.ncbi.nlm.nih.gov/pubmed/15976016?dopt=AbstractPlus ] at mGlu 1  receptors and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1425 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1425  [ http://www.ncbi.nlm.nih.gov/pubmed/11814808?dopt=AbstractPlus ] and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5394 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5394  [ http://www.ncbi.nlm.nih.gov/pubmed/12438526?dopt=AbstractPlus ] at mGlu5 receptors; [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1399 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1399  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1396 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1396  for mGlu 2  and mGlu 3  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/10530814?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10884552?dopt=AbstractPlus ]). Although a number of radioligands have been used to examine binding in native tissues, correlation with individual subtypes is limited. Many pharmacological agents have not been fully tested across all known subtypes of mGlu receptors and may have unappreciated biased or neutral activity at other subtypes [ http://www.ncbi.nlm.nih.gov/pubmed/29514854?dopt=AbstractPlus ]. Potential differences linked to the species ( e.g.  human  versus  rat or mouse) of the receptors and the receptor splice variants are generally not known. The influence of receptor expression level on pharmacology and selectivity has not been controlled for in most studies, particularly those involving functional assays of receptor coupling.\n( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3421  is an antagonist at mGlu 1 , but is an agonist (albeit of reduced efficacy) at mGlu 5  receptors.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1377  also exhibits agonist activity at NMDA glutamate receptors [ http://www.ncbi.nlm.nih.gov/pubmed/9106476?dopt=AbstractPlus ], and is an antagonist at all Group‐III mGluRs with an IC 50  of 30 μ M. A potential novel metabotropic glutamate receptor coupled to phosphoinositide turnover has been observed in rat brain; it is activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5449  (ineffective as an agonist at recombinant Group I metabotropic glutamate receptors), but is resistant to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1378  [ http://www.ncbi.nlm.nih.gov/pubmed/9353394?dopt=AbstractPlus ]. There are also reports of a distinct metabotropic glutamatereceptor coupled tophospholipase D in ratbrain, which does not readily fit into the current classification [ http://www.ncbi.nlm.nih.gov/pubmed/9175608?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8799579?dopt=AbstractPlus ]\nA related class C receptor composed of two distinct subunits, T1R1 + T1R3 is also activated by glutamate and is responsible for umami taste detection.\nAll selective antagonists at metabotropic glutamate receptors are competitive.\nConn PJ  et al . (1997) Pharmacology and functions of metabotropic glutamate receptors.  Annu. Rev. Pharmacol. Toxicol. \n 37 : 205‐237 [ https://www.ncbi.nlm.nih.gov/pubmed/9131252?dopt=AbstractPlus ]\nFerraguti F  et al . (2006) Metabotropic glutamate receptors.  Cell Tissue Res. \n 326 : 483‐504 [ https://www.ncbi.nlm.nih.gov/pubmed/16847639?dopt=AbstractPlus ]\nNicoletti F  et al . (2011) Metabotropic glutamate receptors: from the workbench to the bedside.  Neuropharmacology \n 60 : 1017‐41 [ https://www.ncbi.nlm.nih.gov/pubmed/21036182?dopt=AbstractPlus ]\nNiswender CM  et al . (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease.  Annu. Rev. Pharmacol. Toxicol. \n 50 : 295‐322 [ https://www.ncbi.nlm.nih.gov/pubmed/20055706?dopt=AbstractPlus ]\nPin JP  et al . (2016) Organization and functions of mGlu and GABAB receptor complexes.  Nature \n 540 : 60‐68 [ https://www.ncbi.nlm.nih.gov/pubmed/27905440?dopt=AbstractPlus ]\nRondard P  et al . (2011) The complexity of their activation mechanism opens new possibilities for the modulation of mGlu and GABAB class C G protein‐coupled receptors.  Neuropharmacology \n 60 : 82‐92 [ https://www.ncbi.nlm.nih.gov/pubmed/20713070?dopt=AbstractPlus ]\n\nMotilin receptors ( provisional nomenclature ) are activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1458  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7141 ,  http://www.uniprot.org/uniprot/P12872 ), a 22 amino‐acid peptide derived from a precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7141 ,  http://www.uniprot.org/uniprot/P12872 ), which may also generate a  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5376  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7141 ,  http://www.uniprot.org/uniprot/P12872 ). These receptors promote gastrointestinal motility and are suggested to be responsible for the gastrointestinal prokinetic effects of certain macrolide antibiotics (often called motilides;  e.g.  erythromycin), although for many of these molecules the evidence is sparse.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=297 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4495 ,  http://www.uniprot.org/uniprot/O43193 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1458  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7141 ,  http://www.uniprot.org/uniprot/P12872 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11461914?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15677347?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11781320?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16531413?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1444  [ http://www.ncbi.nlm.nih.gov/pubmed/15764739?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1456  [ http://www.ncbi.nlm.nih.gov/pubmed/10381885?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10381885?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6510  [ http://www.ncbi.nlm.nih.gov/pubmed/23190027?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4035  [ http://www.ncbi.nlm.nih.gov/pubmed/25341626?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19374732?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3511  [1123,  http://www.ncbi.nlm.nih.gov/pubmed/17183187?dopt=AbstractPlus ] – Rabbit Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4036  (p A \n 2  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/18164286?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1466  (pIC 50  8) [ http://www.ncbi.nlm.nih.gov/pubmed/11806718?dopt=AbstractPlus ] – Rabbit Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3794  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10381885?dopt=AbstractPlus ]\nIn terms of structure, the motilin receptor has closest homology with the ghrelin receptor. Thus, the human motilin receptor shares 52% overall amino acid identity with the ghrelin receptor and 86% in the transmembrane regions [ http://www.ncbi.nlm.nih.gov/pubmed/19696113?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17183187?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15764739?dopt=AbstractPlus ]. However, differences between the N‐terminus regions of these receptors means that their cognate peptide ligands do not readily activate each other [ http://www.ncbi.nlm.nih.gov/pubmed/14504130?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19374732?dopt=AbstractPlus ]. In laboratory rodents, the gene encoding the motilin percursor appears to be absent, while the receptor appears to be a pseudogene [ http://www.ncbi.nlm.nih.gov/pubmed/19696113?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21531468?dopt=AbstractPlus ]. Functions of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1458  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7141 ,  http://www.uniprot.org/uniprot/P12872 ) are not usually detected in rodents, although brain and other responses to motilin and the macrolide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1444  have been reported and the mechanism of these actions is obscure [ http://www.ncbi.nlm.nih.gov/pubmed/9441746?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10092986?dopt=AbstractPlus ]. Notably, in some non‐laboratory rodents ( e.g.  the North American kangaroo rat ( Dipodomys ) and mouse ( Microdipodops ) a functional form of motilin may exist but the motilin receptor is non‐functional [ http://www.ncbi.nlm.nih.gov/pubmed/15027861?dopt=AbstractPlus ]. Marked differences in ligand affinities for the motilin receptor in dogs and humans may be explained by significant differences in receptor structure [ http://www.ncbi.nlm.nih.gov/pubmed/23189978?dopt=AbstractPlus ]. Note that for the complex macrolide structures, selectivity of action has often not been rigorously examined and other actions are possible ( e.g.  P2X inhibition by erythromycin; [ http://www.ncbi.nlm.nih.gov/pubmed/10749750?dopt=AbstractPlus ]). Small molecule motilin receptor agonists are now described [ http://www.ncbi.nlm.nih.gov/pubmed/15027861?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19374732?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21544957?dopt=AbstractPlus ]. The motilin receptor does not appear to have constitutive activity [ http://www.ncbi.nlm.nih.gov/pubmed/12907757?dopt=AbstractPlus ]. Although not proven, the existence of biased agonism at the receptor has been suggested [ http://www.ncbi.nlm.nih.gov/pubmed/16531413?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17074305?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24438586?dopt=AbstractPlus ]. A truncated 5‐transmembrane structure has been identified but this is without activity when transfected into a host cell [ http://www.ncbi.nlm.nih.gov/pubmed/10381885?dopt=AbstractPlus ]. Receptor dimerisation has not been reported.\nDe Smet B  et al . (2009) Motilin and ghrelin as prokinetic drug targets.  Pharmacol. Ther. \n 123 : 207‐23 [ https://www.ncbi.nlm.nih.gov/pubmed/19427331?dopt=AbstractPlus ]\nMarrinan SL  etal . (2018) A randomized, double‐blind, placebo‐controlled trial of camicinal in Parkinson's disease.  Mov. Disord. \n 33 : 329‐332 [ https://www.ncbi.nlm.nih.gov/pubmed/29278279?dopt=AbstractPlus ]\nSanger GJ  et al . (2016) Ghrelin and motilin receptors as drug targets for gastrointestinal disorders.  Nat Rev Gastroenterol Hepatol \n 13 : 38‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/26392067?dopt=AbstractPlus ]\n\nNeuromedin U receptors ( provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous 25 amino acid peptide neuromedin U ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1470  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7859 ,  http://www.uniprot.org/uniprot/P48645 ), NmU‐25), a peptide originally isolated from pig spinal cord [ http://www.ncbi.nlm.nih.gov/pubmed/3839674?dopt=AbstractPlus ]. In humans, NmU‐25 appears to be the sole product of a precursor gene ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7859 ,  http://www.uniprot.org/uniprot/P48645 ) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C‐terminal region (particularly the C‐terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1468  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:32203 ,  http://www.uniprot.org/uniprot/Q5H8A3 )) has also been identified as an endogenous agonist [ http://www.ncbi.nlm.nih.gov/pubmed/15635449?dopt=AbstractPlus ]. NmS33 is, as its name suggests, a 33 amino‐acid product of a precursor protein derived from a single gene and contains an amidated Cterminal heptapeptide identical to NmU. NmS‐33 appears to activate NMU receptors with equivalent potency to NmU‐25.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=298 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=299 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4518 ,  http://www.uniprot.org/uniprot/Q9HB89 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16454 ,  http://www.uniprot.org/uniprot/Q9GZQ4 \n Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3524  (p K \n B  7) [ http://www.ncbi.nlm.nih.gov/pubmed/19369576?dopt=AbstractPlus ]\nNMU1 and NMU2 couple predominantly to G q/11  although there is evidence of good coupling to G i/o  [ http://www.ncbi.nlm.nih.gov/pubmed/15331768?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10887190?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17652154?dopt=AbstractPlus ]. NMU1 and NMU2 can be labelled with [ 125 I]‐NmU and [ 125 I]‐NmS (of various species,  e.g.  [ http://www.ncbi.nlm.nih.gov/pubmed/18358099?dopt=AbstractPlus ]),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3858  or  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3863  [ http://www.ncbi.nlm.nih.gov/pubmed/15331768?dopt=AbstractPlus ]. A range of radiolabelled (  125 I‐), fluorescently labelled ( e.g.  Cy3, Cy5, rhodamine and FAM) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4787  labelled versions of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1470  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7859 ,  http://www.uniprot.org/uniprot/P48645 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1468  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:32203 ,  http://www.uniprot.org/uniprot/Q5H8A3 ) are now commercially available.\nBrighton PJ  et al . (2004) Neuromedin U and its receptors: structure, function, and physiological roles.  Pharmacol. Rev. \n 56 : 231‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/15169928?dopt=AbstractPlus ]\nBudhiraja S  et al . (2009) Neuromedin U: physiology, pharmacology and therapeutic potential.  Fundam Clin Pharmacol \n 23 : 149‐57 [ https://www.ncbi.nlm.nih.gov/pubmed/19645813?dopt=AbstractPlus ]\nMitchell JD  et al . (2009) Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S.  Br. J. Pharmacol. \n 158 : 87‐103 [ https://www.ncbi.nlm.nih.gov/pubmed/19519756?dopt=AbstractPlus ]\nNovak CM. (2009) Neuromedin S and U.  Endocrinology \n 150 : 2985‐7 [ https://www.ncbi.nlm.nih.gov/pubmed/19549882?dopt=AbstractPlus ]\n\nThe Neuropeptide FF receptor family contains two subtypes, NPFF1 and NPFF2 ( provisional nomenclature  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]), which exhibit high affinities for neuropeptide FF ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) and RFamide related peptides (RFRP: precursor genesymbol  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ). NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density in the superficial layers of the mammalian spinal cord where it is involved in nociception and modulation of opioid functions.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=300 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=301 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17425 ,  http://www.uniprot.org/uniprot/Q9GZQ6 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4525 ,  http://www.uniprot.org/uniprot/Q9Y5X5 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5340  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4016  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ) > FMRF http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1479  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3735  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3736  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3665  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29982 ,  http://www.uniprot.org/uniprot/P83859 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1873  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) [ http://www.ncbi.nlm.nih.gov/pubmed/17011599?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3735  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1479  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1873  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) > FMRF,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3665  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29982 ,  http://www.uniprot.org/uniprot/P83859 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3736  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) [ http://www.ncbi.nlm.nih.gov/pubmed/17011599?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1479  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) [ http://www.ncbi.nlm.nih.gov/pubmed/17011599?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12421602?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12242085?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4016  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7  [ http://www.ncbi.nlm.nih.gov/pubmed/12421602?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17337079?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12242085?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1479  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12421602?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11325787?dopt=AbstractPlus ] Selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1489  [ http://www.ncbi.nlm.nih.gov/pubmed/16129413?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4020  [ http://www.ncbi.nlm.nih.gov/pubmed/20354177?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1486  (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/16407169?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4017  (p K \n i  7.7–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/20354177?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4018  (p K \n i  7.4–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/20354177?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1484  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12421602?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4019  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/19682524?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3797  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17011599?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1488  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12242085?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4021  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/19682524?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3797  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17011599?dopt=AbstractPlus ]\nAn orphan receptor  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4523  ( http://www.uniprot.org/uniprot/Q9NYM4 ) shows sequence similarities with NPFF1, NPFF2, PrRP and QRFP receptors. The antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1486  is selective for NPFF receptors, but does not distinguish between the NPFF1 and NPFF2 subtypes (p K i 7.1 and 7.2, respectively, [ http://www.ncbi.nlm.nih.gov/pubmed/16407169?dopt=AbstractPlus ]).\nMoulédous L  et al . (2010) Opioid‐modulating properties of the neuropeptide FF system.  Biofactors \n 36 : 423‐9 [ https://www.ncbi.nlm.nih.gov/pubmed/20803521?dopt=AbstractPlus ]\nVyas N  et al . (2006) Structure‐activity relationships of neuropeptide FF and related peptidic and non‐peptidic derivatives.  Peptides \n 27 : 990‐6 [ https://www.ncbi.nlm.nih.gov/pubmed/16490282?dopt=AbstractPlus ]\nYang HY  et al . (2008) Modulatory role of neuropeptide FF system in nociception and opiate analgesia.  Neuropeptides \n 42 : 1‐18 [ https://www.ncbi.nlm.nih.gov/pubmed/17854890?dopt=AbstractPlus ]\n\nThe neuropeptide S receptor (NPS,  provisional nomenclature  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) responds to the 20 amino‐acid peptide neuropeptide S derived from a precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:33940 ,  http://www.uniprot.org/uniprot/P0C0P6 ).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=302 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:23631 ,  http://www.uniprot.org/uniprot/Q6W5P4 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1490  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:33940 ,  http://www.uniprot.org/uniprot/P0C0P6 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15312648?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9167  [ http://www.ncbi.nlm.nih.gov/pubmed/25692025?dopt=AbstractPlus ] – Mouse Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9168  (p A \n 2  9) [ http://www.ncbi.nlm.nih.gov/pubmed/23761908?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5813  (p A \n 2  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/20172007?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7929  [ http://www.ncbi.nlm.nih.gov/pubmed/18555684?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1493  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15312648?dopt=AbstractPlus ]\nMultiple single‐nucleotide polymorphisms (SNP) and several splice variants have been identified in the human NPS receptor. The most interesting of these is an Asn‐Ile exchange at position 107 (Asn 107 Ile). The human NPS receptor Asn 107 Ile displayed similar binding affinity buthigher NPSpotency (by approx. 10‐fold) than human NPS receptor Asn107 [ http://www.ncbi.nlm.nih.gov/pubmed/16144971?dopt=AbstractPlus ]. Several epidemiological studies reported an association between Asn 107 Ile receptor variant and susceptibility to panic disorders [ http://www.ncbi.nlm.nih.gov/pubmed/20603625?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20705147?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17669576?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20628342?dopt=AbstractPlus ]. The SNP Asn 107 Ile has also been linked to sleep behavior [ http://www.ncbi.nlm.nih.gov/pubmed/17903308?dopt=AbstractPlus ], inflammatory bowel disease [ http://www.ncbi.nlm.nih.gov/pubmed/17854592?dopt=AbstractPlus ], schizophrenia [ http://www.ncbi.nlm.nih.gov/pubmed/22078257?dopt=AbstractPlus ], increased impulsivity and ADHD symptoms [ http://www.ncbi.nlm.nih.gov/pubmed/23325374?dopt=AbstractPlus ]. Interestingly, a carboxy‐terminal splice variant of human NPS receptor was found to be overexpressed in asthmatic patients [ http://www.ncbi.nlm.nih.gov/pubmed/15073379?dopt=AbstractPlus ].\nGrund T  et al . (2019) Brain neuropeptide S: via GPCR activation to a powerful neuromodulator of socio‐emotional behaviors.  Cell Tissue Res. \n 375 : 123‐132 [ https://www.ncbi.nlm.nih.gov/pubmed/30112573?dopt=AbstractPlus ]\nGuerrini R  et al . (2010) Neurobiology, pharmacology, and medicinal chemistry of neuropeptide S and its receptor.  Med Res Rev \n 30 : 751‐77 [ https://www.ncbi.nlm.nih.gov/pubmed/19824051?dopt=AbstractPlus ]\nRuzza C  et al . (2017) Neuropeptide S receptor ligands: a patent review (2005‐2016).  Expert Opin Ther Pat \n 27 : 347‐362 [ https://www.ncbi.nlm.nih.gov/pubmed/27788040?dopt=AbstractPlus ]\nXu YL  et al . (2004) Neuropeptide S: a neuropeptide promoting arousal and anxiolytic‐like effects.  Neuron \n 43 : 487‐497 [ https://www.ncbi.nlm.nih.gov/pubmed/15312648?dopt=AbstractPlus ]\n\nThe neuropeptide BW receptor 1 (NPBW1,  provisional nomenclature  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) is activated by two 23‐amino‐acid peptides, neuropeptide W ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1495  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 )) and neuropeptide B ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1501  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 )) [ http://www.ncbi.nlm.nih.gov/pubmed/12118011?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12130646?dopt=AbstractPlus ]. C‐terminally extended forms of the peptides ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1496  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1502  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 )) also activate NPBW1[ http://www.ncbi.nlm.nih.gov/pubmed/12401809?dopt=AbstractPlus ]. Unique to both forms of neuropeptide B is the N‐terminal bromination of the first tryptophan residue, and it is from this post‐translational modification that the nomenclature NPB is derived. These peptides were first identified from bovine hypothalamus and therefore are classed as neuropeptides. Endogenous variants of the peptides without the N‐terminal bromination,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1499  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1500  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ), were not found to be major components of bovine hypothalamic tissue extracts. The NPBW2 receptor is activated by the short and C‐terminal extended forms of neuropeptide W and neuropeptide B [ http://www.ncbi.nlm.nih.gov/pubmed/12401809?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=303 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=304 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4522 ,  http://www.uniprot.org/uniprot/P48145 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4530 ,  http://www.uniprot.org/uniprot/P48146 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1502  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1501  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1495  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1496  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12401809?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1495  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1496  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30509 ,  http://www.uniprot.org/uniprot/Q8N729 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1502  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1501  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30099 ,  http://www.uniprot.org/uniprot/Q8NG41 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12401809?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3855  [ http://www.ncbi.nlm.nih.gov/pubmed/17486669?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3856  [ http://www.ncbi.nlm.nih.gov/pubmed/17486669?dopt=AbstractPlus ] – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1497  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15261118?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1497  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12130646?dopt=AbstractPlus ]\nPotency measurements were conducted with heterologously‐expressed receptors with a range of 0.14‐0.57 nM (NPBW1) and 0.98‐21 nM (NPBW2).\nNPBW1 ‐/‐  mice show changes in social behavior, suggesting that the NPBW1pathway may have animportant role in theemotional responses of social interaction [ http://www.ncbi.nlm.nih.gov/pubmed/21390312?dopt=AbstractPlus ].\nFor a review of the contribution of neuropeptide B/W to social dominance, see Watanabe and Yamamoto, 2015 [ http://www.ncbi.nlm.nih.gov/pubmed/26136644?dopt=AbstractPlus ]. It has been reported that neuropeptide W may have a key role in the gating of stressful stimuli when mice are exposed to novel environments [ http://www.ncbi.nlm.nih.gov/pubmed/27140610?dopt=AbstractPlus ].\nTwo antagonists have been discovered and reported to have affinity for NPBW1, ML181 and ML250, the latter exhibiting improved selectivity (100 fold) for NPBW1 compared to MCH1 receptors [ http://www.ncbi.nlm.nih.gov/pubmed/23762933?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22834040?dopt=AbstractPlus ]. Computational insights into the binding of antagonists to this receptor have also been described [ http://www.ncbi.nlm.nih.gov/pubmed/24938207?dopt=AbstractPlus ].\nSakurai T. (2013) NPBWR1 and NPBWR2: Implications in Energy Homeostasis, Pain, and Emotion.  Front Endocrinol (Lausanne) \n 4 : 23 [ https://www.ncbi.nlm.nih.gov/pubmed/23515889?dopt=AbstractPlus ]\nSingh G  et al . (2006) Neuropeptide B and W: neurotransmitters in an emerging G‐protein‐coupled receptor system.  Br. J. Pharmacol. \n 148 : 1033‐41 [ https://www.ncbi.nlm.nih.gov/pubmed/16847439?dopt=AbstractPlus ]\n\nNeuropeptide Y (NPY) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Neuropeptide Y Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/9549761?dopt=AbstractPlus ]) are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7955 ,  http://www.uniprot.org/uniprot/P01303 ), neuropeptide Y‐(3‐36),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1514  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9748 ,  http://www.uniprot.org/uniprot/P10082 ), PYY‐(3‐36) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1512  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9327 ,  http://www.uniprot.org/uniprot/P01298 ) (PP). The receptor originally identified as the Y3 receptor has been identified as the  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=71  (originally named LESTR, [ http://www.ncbi.nlm.nih.gov/pubmed/8276799?dopt=AbstractPlus ]). The y6 receptor is a functional gene product in mouse, absent in rat, but contains a frame‐shift mutation in primates producing a truncated non‐functional gene [ http://www.ncbi.nlm.nih.gov/pubmed/8641440?dopt=AbstractPlus ]. Many of the agonists exhibit differing degrees of selectivity dependent on the species examined. For example, the potency of PP is greater at the rat Y4 receptor than at the human receptor [ http://www.ncbi.nlm.nih.gov/pubmed/9802391?dopt=AbstractPlus ]. In addition, many agonists lack selectivity for individual subtypes, but can exhibit comparable potency against pairs of NPY receptor subtypes, or have not been examined for activity at all subtypes. [ 125 I]‐PYY or [ 125 I]‐NPY can be used to label Y 1 , Y 2 , Y5 and y 6  subtypes non‐selectively, while [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3921  may be used to label Y5 receptors preferentially (note that cPP denotes chicken peptide sequence and hPP is the human sequence).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=305 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=306 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=307 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=308 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=683 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7956 ,  http://www.uniprot.org/uniprot/P25929 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7957 ,  http://www.uniprot.org/uniprot/P49146 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9329 ,  http://www.uniprot.org/uniprot/P50391 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7958 ,  http://www.uniprot.org/uniprot/Q15761 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7959 ,  http://www.uniprot.org/uniprot/Q99463 \n Potency order of endogenous ligands neuropeptide Y = peptide YY ≫ pancreatic polypeptide peptide YY = peptide YY(3‐36) = neuropeptide Y = neuropeptide Y(3‐36) ≫ pancreatic polypeptide pancreatic polypeptide ≫ neuropeptide Y = peptide YY neuropeptide Y > peptide YY > pancreatic polypeptide neuropeptide Y = peptide YY > pancreatic polypeptide Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7955 ,  http://www.uniprot.org/uniprot/P01303 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1514  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9748 ,  http://www.uniprot.org/uniprot/P10082 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1517 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9748 ,  http://www.uniprot.org/uniprot/P10082 ) [ http://www.ncbi.nlm.nih.gov/pubmed/8632753?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7592910?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7955 ,  http://www.uniprot.org/uniprot/P01303 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3627 ) ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7955 ,  http://www.uniprot.org/uniprot/P01303 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1514  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9748 ,  http://www.uniprot.org/uniprot/P10082 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1512  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9327 ,  http://www.uniprot.org/uniprot/P01298 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7592911?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7493937?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16807358?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8643460?dopt=AbstractPlus ] – – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1545  [ http://www.ncbi.nlm.nih.gov/pubmed/8590988?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1527 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3848 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1546 \n – – – – Selective agonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1522  [ http://www.ncbi.nlm.nih.gov/pubmed/12069595?dopt=AbstractPlus ] – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1528  (pIC 50  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9806339?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1485  (p K \n i  8.1–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7562541?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7562543?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1547  (pIC 50  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/10611450?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3504  (pIC 50  6.9–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/14617685?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1565  (p K \n i  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/10872822?dopt=AbstractPlus ] – Selective allosteric modulators – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8494  (Positive) [ http://www.ncbi.nlm.nih.gov/pubmed/27294784?dopt=AbstractPlus ] – – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3474  (Antagonist) (p K \n d  8.7), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3762  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3802  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3800  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3921  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15337369?dopt=AbstractPlus ] – Rat Comments Note that Pro 34 ‐containing NPY and PYY can also bind Y 4  and Y 5  receptors, so strictly speaking are not selective, but are the ’preferred’ agonists. – – – –\nThe Y 1  agonists indicated are selective relative to Y 2  receptors.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1485  is selective relative to Y 2 , Y 4  and Y 5  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/8700207?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3903 ) is Y 2  selective relative to Y 1  and Y 5  receptors. PYY‐(3‐36) is Y 2  selective relative to Y 1  receptors. Note that Pro34‐containing NPY and PYY can also bind Y 4  and Y 5 , thus they are selective only relative to Y 2 . The y 6  receptor is a pseudogene in humans, but is functional in mouse, rabbit and some other mammals.\nBowers ME  et al . (2012) Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y.  Physiol. Behav. \n 107 : 699‐710 [ https://www.ncbi.nlm.nih.gov/pubmed/22429904?dopt=AbstractPlus ]\nMichel MC  et al . (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors.  Pharmacol. Rev. \n 50 : 143‐150 [ https://www.ncbi.nlm.nih.gov/pubmed/9549761?dopt=AbstractPlus ]\nPedragosa‐Badia X  et al . (2013) Neuropeptide Y receptors: how to get subtype selectivity.  Front En docrinol (Lausanne) \n 4 : 5 [ https://www.ncbi.nlm.nih.gov/pubmed/23382728?dopt=AbstractPlus ]\nZhang L  et al . (2011) The neuropeptide Y system: pathophysiological and therapeutic implications in obesity and cancer.  Pharmacol. Ther. \n 131 : 91‐113 [ https://www.ncbi.nlm.nih.gov/pubmed/21439311?dopt=AbstractPlus ]\n\nNeurotensin receptors ( nomenclature as recommended by \n NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous tridecapeptide neurotensin (pGlu‐Leu‐Tyr‐Glu‐Asn‐Lys‐Pro‐Arg‐Arg‐Pro‐Tyr‐Ile‐Leu) derived from a precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8038 ,  http://www.uniprot.org/uniprot/30990 ), which also generates neuromedin N, an agonist at the NTS 2  receptor.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3830 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1574 ) may be used to label NTS 1  and NTS 2  receptors at 0.1‐0.3 and 3‐5 nM concentrations respectively.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=309 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=310 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8039 ,  http://www.uniprot.org/uniprot/P30989 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8040 ,  http://www.uniprot.org/uniprot/O95665 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1579  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8038 ,  http://www.uniprot.org/uniprot/P30990 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1578  {Mouse, Rat} [ http://www.ncbi.nlm.nih.gov/pubmed/9283723?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1579  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8038 ,  http://www.uniprot.org/uniprot/P30990 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1578  {Mouse, Rat} [ http://www.ncbi.nlm.nih.gov/pubmed/8795617?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1570  [ http://www.ncbi.nlm.nih.gov/pubmed/12869647?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1586  [ http://www.ncbi.nlm.nih.gov/pubmed/8795617?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11723247?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1582  (pIC 50  7.5–8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9023294?dopt=AbstractPlus ] – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1583  (Antagonist) (p K \n d  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/7746272?dopt=AbstractPlus ] – Rat –\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1579  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8038 ,  http://www.uniprot.org/uniprot/P30990 ) appears to be a lowefficacy agonist at the NTS 2  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/9851594?dopt=AbstractPlus ], while the NTS 1  receptor antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1582  is an agonist at NTS 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/9851594?dopt=AbstractPlus ]. An additional protein, provisionally termed NTS 3  (also known as NTR3, gp95 and sortilin;  http://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134243;r=1:109852192‐109940573 ), has been suggested to bind lipoprotein lipase and mediate its degradation [ http://www.ncbi.nlm.nih.gov/pubmed/10085125?dopt=AbstractPlus ]. It has been reported to interact with the NTS 1  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/12360476?dopt=AbstractPlus ] and the NTS 2  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/19891061?dopt=AbstractPlus ], and has beenimplicated in hormone trafficking and/or neurotensin uptake. A splice variant of the NTS 2  receptor bearing 5 transmembrane domains has been identified in mouse [ http://www.ncbi.nlm.nih.gov/pubmed/9001400?dopt=AbstractPlus ] and later in rat [ http://www.ncbi.nlm.nih.gov/pubmed/15637074?dopt=AbstractPlus ].\nBoules M  et al . (2013) Diverse roles of neurotensin agonists in the central nervous system.  Front Endocrinol (Lausanne) \n 4 : 36  https://www.ncbi.nlm.nih.gov/pubmed/23526754?dopt=AbstractPlus\nMazella J  et al . (2012) Neurotensin and its receptors in the control of glucose homeostasis.  Front Endocrinol (Lausanne) \n 3 : 143  https://www.ncbi.nlm.nih.gov/pubmed/23230428?dopt=AbstractPlus\nMyers RM  et al . (2009) Cancer, chemistry, and the cell: molecules that interact with the neurotensin receptors.  ACS Chem. Biol. \n 4 : 503‐25  https://www.ncbi.nlm.nih.gov/pubmed/19462983?dopt=AbstractPlus\nOuyang Q  et al . (2017) Oncogenic role of neurotensin and neurotensin receptors in various cancers.  Clin. Exp. Pharmacol. Physiol. \n 44 : 841‐846  https://www.ncbi.nlm.nih.gov/pubmed/28556374?dopt=AbstractPlus\n\nOpioid and opioid‐like receptors are activated by a variety of endogenous peptides including [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1614  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) (met),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1613  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) (leu),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ) (β‐end),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3737  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1620  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ) (dynA),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1622  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ) (dynB),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3669  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ) (Big dyn),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9163 ,  http://www.uniprot.org/uniprot/Q13519 ) (N/OFQ);  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1623  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3668  are also potential endogenous peptides. The Greek letter nomenclature for the opioid receptors,  μ ,  δ  and  κ , is well established, and  NC‐IUPHAR  considers this nomenclature appropriate, along with the symbols spelled out (mu, delta, and kappa), and the acronyms, MOP, DOP, and KOP. [ http://www.ncbi.nlm.nih.gov/pubmed/24528283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8981566?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]. The human N/OFQ receptor, NOP, is considered ’opioid‐related’ rather than opioid because, while it exhibits a high degree of structural homology with the conventional opioid receptors [ http://www.ncbi.nlm.nih.gov/pubmed/8137918?dopt=AbstractPlus ], it displays a distinct pharmacology. Currently there are numerous clinically used drugs, such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1627  and many other opioid analgesics, as well as antagonists such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638 , however only for the  μ  receptor.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=317 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=318 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8153 ,  http://www.uniprot.org/uniprot/P41143 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8154 ,  http://www.uniprot.org/uniprot/P41145 \n Principal endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1613  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1614  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3669  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1620  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8820 ,  http://www.uniprot.org/uniprot/P01213 ) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1607  [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1625  [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1602  [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ] – Sub/family‐selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9294  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21177476?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9294  [ http://www.ncbi.nlm.nih.gov/pubmed/21177476?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9006  [ http://www.ncbi.nlm.nih.gov/pubmed/18069089?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9002  [ http://www.ncbi.nlm.nih.gov/pubmed/18788723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9004  [ http://www.ncbi.nlm.nih.gov/pubmed/18788723?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1608  [ http://www.ncbi.nlm.nih.gov/pubmed/6310598?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4060  [ http://www.ncbi.nlm.nih.gov/pubmed/2544892?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9003  [ http://www.ncbi.nlm.nih.gov/pubmed/19694468?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1611  [ http://www.ncbi.nlm.nih.gov/pubmed/8035418?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9178661?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1652  [ http://www.ncbi.nlm.nih.gov/pubmed/14718611?dopt=AbstractPlus ,  1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/6129321?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7869844?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9262330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1646  [ http://www.ncbi.nlm.nih.gov/pubmed/2178014?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14613319?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1655  [ http://www.ncbi.nlm.nih.gov/pubmed/2986999?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2986999?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1666  [ http://www.ncbi.nlm.nih.gov/pubmed/15869877?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12192085?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9838  (p K \n i  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/22194444?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/29524334?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1639  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638  (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1670  (p K \n i  9.1–10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9262330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1628  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1639  (p K \n i  8.4–9.4) [ 1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638  (p K \n i  7.6–8.6) [ 1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7869844?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9262330?dopt=AbstractPlus ] Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8870  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12801588?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8870  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25635572?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1640  (p K \n i  10) [ http://www.ncbi.nlm.nih.gov/pubmed/1851833?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1641  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/2832195?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1637  (Inverse agonist) (p K \n i  9) [ http://www.ncbi.nlm.nih.gov/pubmed/8230106?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1642  (p K \n i  8.9–11) [ 1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/2444704?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7869844?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9262330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1669  (p K \n i  9.7–9.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10822054?dopt=AbstractPlus ,  1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/10893314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7362  (p K \n i  9–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/23976952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11495579?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25635572?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3829  (Antagonist) (p K \n d  10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/1313133?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9065  (Selective Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1329092?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1612  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1313812?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3819  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2986120?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3816  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1313131?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3828  (Antagonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9696425?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1612  (Antagonist) (p K \n d  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/1313812?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1656  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2986999?dopt=AbstractPlus ,  1671 ,  http://www.ncbi.nlm.nih.gov/pubmed/7624359?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3475  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11239918?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=319 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=320 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8156 ,  http://www.uniprot.org/uniprot/P35372 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8155 ,  http://www.uniprot.org/uniprot/P41146 \n Potential endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1623 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3668 \n – Principal endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9201 ,  http://www.uniprot.org/uniprot/P01189 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1614  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1613  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8831 ,  http://www.uniprot.org/uniprot/P01210 ) – Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1681  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9163 ,  http://www.uniprot.org/uniprot/Q13519 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9413015?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12070757?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369464?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7595  [ http://www.ncbi.nlm.nih.gov/pubmed/12502358?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7082  [ http://www.ncbi.nlm.nih.gov/pubmed/19282177?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1626  [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1670  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5458  [ http://www.ncbi.nlm.nih.gov/pubmed/11585443?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9838  [ http://www.ncbi.nlm.nih.gov/pubmed/22194444?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/29524334?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1671  [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7477  [ http://www.ncbi.nlm.nih.gov/pubmed/17656655?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7221  [ http://www.ncbi.nlm.nih.gov/pubmed/11585443?dopt=AbstractPlus ] – Sub/family‐selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9294  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21177476?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8866  [ http://www.ncbi.nlm.nih.gov/pubmed/24713140?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9294  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21177476?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3534  [ http://www.ncbi.nlm.nih.gov/pubmed/21215785?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1647  [ http://www.ncbi.nlm.nih.gov/pubmed/6263640?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7215  [ http://www.ncbi.nlm.nih.gov/pubmed/15454210?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1627  [ http://www.ncbi.nlm.nih.gov/pubmed/2549383?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1671  [ http://www.ncbi.nlm.nih.gov/pubmed/6313901?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1682  [ http://www.ncbi.nlm.nih.gov/pubmed/12070757?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9191955?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12967935?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10369464?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1680  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9353393?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12967935?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8868  [ http://www.ncbi.nlm.nih.gov/pubmed/18492950?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1684  [ http://www.ncbi.nlm.nih.gov/pubmed/10758169?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11006485?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9747  [ http://www.ncbi.nlm.nih.gov/pubmed/29232769?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1639  (p K \n i  9.1–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/24973897?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1628  (p K \n i  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1629  (p K i 8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638  (p K \n i  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7563  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/19282177?dopt=AbstractPlus ] – Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8870  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25635572?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8870  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/25635572?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7471  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/18313920?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7209  (p K \n i  8.8–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21621410?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1635  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/6313901?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9686407?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1694  (p K \n i  10.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12010780?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9462  (p K \n i  10) [ http://www.ncbi.nlm.nih.gov/pubmed/24678969?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7361  (p K \n i  9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/19445927?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1693  (p K \n i  9.2–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/17329552?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14593080?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1691  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10602690?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9159  (Neutral) (p K \n B  6) [ http://www.ncbi.nlm.nih.gov/pubmed/23754417?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9156  (Positive) (p K \n B  5.7) [ http://www.ncbi.nlm.nih.gov/pubmed/23754417?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9160  (Neutral) (p K \n B  5.7) [ http://www.ncbi.nlm.nih.gov/pubmed/23754417?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9157  (Positive) (p K \n B  5.3) [ http://www.ncbi.nlm.nih.gov/pubmed/23754417?dopt=AbstractPlus ] – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1612  (Antagonist) (p K \n d  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8114680?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3815  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/8114680?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3832  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/3030778?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1688  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9353393?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8849681?dopt=AbstractPlus ]\nThree naloxone‐sensitive opioid receptor genes havebeen identified in humans, and while the  μ ‐receptor in particular may be subject to extensive alternative splicing [ http://www.ncbi.nlm.nih.gov/pubmed/24076545?dopt=AbstractPlus ], these putative isoforms have not been correlated with any of the subtypesof receptor proposed inyears past. Opioid receptors may heterodimerize with each other or with other 7TM receptors [ http://www.ncbi.nlm.nih.gov/pubmed/10385123?dopt=AbstractPlus ], and give rise to complexes with a unique pharmacology, however, evidence for such heterodimers in native cells is equivocal and the consequences of this heterodimerization for signalling remains largely unknown. For  μ ‐opioid receptors at least, dimerization does not seem to be required for signalling [ http://www.ncbi.nlm.nih.gov/pubmed/19542234?dopt=AbstractPlus ]. A distinct met‐enkephalin receptor lacking structural resemblance to the opioid receptors listed has been identified ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15768 ,  http://www.uniprot.org/uniprot/9NZT2 ) and termed an  o pioid growth  f actor  r eceptor [ http://www.ncbi.nlm.nih.gov/pubmed/11890982?dopt=AbstractPlus ].\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1623  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3668  have been identified as highly selective, putative endogenous agonists for the  μ ‐opioid receptor. At present, however, the mechanisms for endomorphin synthesis  in vivo  have not been established, and there is no gene identified that encodes for either. Thus, the status of these peptides as endogenous ligands remains unproven.\nTwo areas of increasing importance in defining opioid receptor function are the presence of functionally relevant single nucleotide polymorphisms in human  μ ‐receptors [ http://www.ncbi.nlm.nih.gov/pubmed/19116204?dopt=AbstractPlus ] and the identification of biased signalling by opioid receptor ligands, in particular, compounds previously characterized as antagonists [ http://www.ncbi.nlm.nih.gov/pubmed/17702750?dopt=AbstractPlus ]. Pathway bias for agonists makes general rank orders of potency and efficacy somewhat obsolete, so these do not appear in the table. As ever, the mechanisms underlying the acute and long term regulation of opiod receptor function are the subject of intense investigation and debate.\nThe richness of opioid receptor pharmacology has been enhanced with the recent discovery of allosteric modulators of  μ  and  δ  receptors, notably thepositive allosteric modulators and silent allosteric “antagonists” outlined in [ http://www.ncbi.nlm.nih.gov/pubmed/23754417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25901762?dopt=AbstractPlus ]. Negative allosteric modulation of opioid receptors has been previously suggested [ http://www.ncbi.nlm.nih.gov/pubmed/16489449?dopt=AbstractPlus ], whether all compounds are acting at a similar site remains to be established.\nButelman ER  et al . (2012)  κ ‐opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction.  Trends Neurosci. \n 35 : 587‐96  https://www.ncbi.nlm.nih.gov/pubmed/22709632?dopt=AbstractPlus\nCox BM  et al . (2015) Challenges for opioid receptor nomenclature: IUPHAR Review 9.  Br. J. Pharmacol. \n 172 : 317‐23  https://www.ncbi.nlm.nih.gov/pubmed/24528283?dopt=AbstractPlus\nPradhan AA  et al . (2011) The delta opioid receptor: an evolving target for the treatment of brain disorders.  Trends Pharmacol. Sci. \n 32 : 581‐90  https://www.ncbi.nlm.nih.gov/pubmed/21925742?dopt=AbstractPlus\nWilliams JT  et al . (2013) Regulation of  μ ‐opioid receptors: desensitization, phosphorylation, internalization, and tolerance.  Pharmacol. Rev. \n 65 : 223‐54  https://www.ncbi.nlm.nih.gov/pubmed/23321159?dopt=AbstractPlus\n\nOrexin receptors  (nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Orexin receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous polypeptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1697  ( https://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:4847 ,  http://www.uniprot.org/uniprot/O43612 )and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1699  ( https://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:4847 , http://www.uniprot.org/uniprot/O43612 ) (also known as hypocretin‐1 and ‐2; 33 and 28 aa) derived from a common precursor,  https://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:4847 , by proteolytic cleavage and some typical peptide modifications [ http://www.ncbi.nlm.nih.gov/pubmed/9491897?dopt=AbstractPlus ]. Currently the only orexin receptor ligand in clinical use is  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2890 ,whichisused as a hypnotic. Orexin receptor crystal structures have been solved [ http://www.ncbi.nlm.nih.gov/pubmed/26950369?dopt=AbstractPlus , http://www.ncbi.nlm.nih.gov/pubmed/25533960?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=321 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=322 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4848 ,  http://www.uniprot.org/uniprot/O43613 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4849 ,  http://www.uniprot.org/uniprot/O43614 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1697  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4847 ,  http://www.uniprot.org/uniprot/O43612 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1699 ,  http://www.uniprot.org/uniprot/O43612 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1697  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4847 ,  http://www.uniprot.org/uniprot/O43612 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1699 ,  http://www.uniprot.org/uniprot/O43612 ) Selective agonists – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700  [ http://www.ncbi.nlm.nih.gov/pubmed/12467628?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21362456?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9305  [ http://www.ncbi.nlm.nih.gov/pubmed/26267383?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30194937?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10277  [ http://www.ncbi.nlm.nih.gov/pubmed/28507129?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28507129?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4461  (p K \n i  9.3–9.6) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20565075?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2890  (p K \n i  8.7–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23692283?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4460  (p K \n i  8.4–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22019562?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9304  (p K \n i  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/18207395?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2886  (p K \n i  7.8–8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22796453?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20404073?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10280  (p K \n i  7.6–8) [ http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4461  (p K \n i  8.9–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20565075?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9304  (p K \n i  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/18207395?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2890  (p K \n i  8.9–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23692283?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10280  (p K \n i  8.5–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4460  (p K i 8.9–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22019562?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9136  (70–300‐fold selective) (p K \n i  8.7–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/14691055?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20404073?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1703  (50–150‐fold selective) (p K \n i  7.2–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/14691055?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11459658?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22079339?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11250867?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1704  (60–80‐fold selective) (p K \n i  7.2–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/14691055?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23692283?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4037  (300–3000‐fold selective) (p K \n i  8.4–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20404073?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23692283?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21679703?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1701  (200–800‐fold selective) (p K \n i  7.7–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/20565075?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15261275?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4038  (p K \n i  6.9–7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/18207395?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14643355?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1706 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1706  (Antagonist) (p K \n d  8.3–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/14691055?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20404073?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465  (Antagonist) (p K \n d  8.6–8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9464 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9464  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/26582739?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25132134?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9491897?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465  (Selective Antagonist) (p K \n d  8.9–9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20404073?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9466 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9466  (Selective Antagonist) (p K \n d  9.2–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/19542319?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9467 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9467  (Selective Antagonist) (p K \n d  8.6–9) [ http://www.ncbi.nlm.nih.gov/pubmed/19751316?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9464 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9464  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/26582739?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25132134?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9491897?dopt=AbstractPlus ]\nThe primary coupling of orexin receptors to G q/11  proteins is rather speculative and based on the strong activation of phospholipase C, though recent studies in recombinant cells also stress the importance of G q/11  [ http://www.ncbi.nlm.nih.gov/pubmed/27237973?dopt=AbstractPlus ]. Coupling of both receptors to G i/o  and Gs has also been reported [ http://www.ncbi.nlm.nih.gov/pubmed/15687100?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23902572?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23848055?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11600545?dopt=AbstractPlus ]. For most native cellular responses observed, the G protein pathway is unknown. The relative potency order of endogenous ligands depends on the cellular signal transduction machinery [ http://www.ncbi.nlm.nih.gov/pubmed/23034387?dopt=AbstractPlus ]. Similarly, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700 ] http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1700 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9305  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10277  may show variable selectivity for OX 2  receptors and are also likely to activate OX 1  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/21362456?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30194937?dopt=AbstractPlus ]. Many antagonists and radioligands are not well‐characterized, and thus the affinities are uncertain. Among radioligands, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1706 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1706 , [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9467 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9467  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9465  are commercially available. [ 3 H]‐TCS 1102 (pK d/OX1  8.2, pK d/OX2  9.0) [ http://www.ncbi.nlm.nih.gov/pubmed/24376396?dopt=AbstractPlus ] and Rhodamine Green‐orexinA [ http://www.ncbi.nlm.nih.gov/pubmed/11266181?dopt=AbstractPlus ] are also useful radioligand tools. Orexin receptors have been reported to be able to form complexes with each other and some other GPCRs as well as  σ 1 receptors, which might affect the signaling and pharmacology [ http://www.ncbi.nlm.nih.gov/pubmed/27909990?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25926444?dopt=AbstractPlus ]. Loss‐of‐function mutations in the gene encoding the OX 2  receptor underlie canine hereditary narcolepsy [ http://www.ncbi.nlm.nih.gov/pubmed/10458611?dopt=AbstractPlus ]. Antagonists of the orexin receptors are the focus of major drug discovery efforts for their potential to treat insomnia and other disorders of wakefulness [ http://www.ncbi.nlm.nih.gov/pubmed/26317591?dopt=AbstractPlus ], while agonists would likely be useful in human narcolepsy.\nBaimel C  et al . (2015) Orexin/hypocretin role in reward: implications for opioid and other addictions.  Br. J. Pharmacol. \n 172 : 334‐48 [ https://www.ncbi.nlm.nih.gov/pubmed/24641197?dopt=AbstractPlus ]\nBurdakov D. (2018) Reactive and predictive homeostasis: Roles of orexin/hypocretin neurons.  Neuropharmacology  [ https://www.ncbi.nlm.nih.gov/pubmed/30347195?dopt=AbstractPlus ]\nKukkonen JP. (2013) Physiology of the orexinergic/hypocretinergic system: a revisit in 2012.  Am. J. Physiol., Cell Physiol. \n 304 : C2‐32 [ https://www.ncbi.nlm.nih.gov/pubmed/23034387?dopt=AbstractPlus ]\nLi SB  et al . (2016) Hypocretins, Neural Systems, Physiology, and Psychiatric Disorders.  Curr Psychiatry Rep \n 18 : 7 [ https://www.ncbi.nlm.nih.gov/pubmed/26733323?dopt=AbstractPlus ]\nMahler SV  et al . (2014) Motivational activation: a unifying hypothesis of orexin/hypocretin function.  Nat. Neurosci. \n 17 : 1298‐303 [ https://www.ncbi.nlm.nih.gov/pubmed/25254979?dopt=AbstractPlus ]\n\nNomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=162 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4531 ,  http://www.uniprot.org/uniprot/Q96P68 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3636  [ http://www.ncbi.nlm.nih.gov/pubmed/15141213?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ]\nDavenport AP  et al . (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein‐coupled receptor list: recommendations for new pairings with cognate ligands.  Pharmacol. Rev. \n 65 : 967‐86 [ https://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]\nGrimm PR and Welling PA (2017) alpha‐Ketoglutarate drives electroneutral NaCl reabsorption in intercalated cells by activating a G‐protein coupled receptor.  Oxgr1. Curr. Opin. Nephrol. Hypertens. \n 26 : 426‐433 [ https://www.ncbi.nlm.nih.gov/pubmed/28771454 ]\n\nP2Y receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on P2Y Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/12559763?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16968944?dopt=AbstractPlus ]) are activated by the endogenous ligands  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1783 . The relationship of many of the cloned receptors to endogenously expressed receptors is not yet established and so it might be appropriate to use wording such as ’ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734 ‐preferring (or  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 ‐,  etc .) P2Y receptor’ or ’P2Y 1 ‐like’,  etc. , until further, as yet undefined, corroborative criteria can be applied [ 271 ,  http://www.ncbi.nlm.nih.gov/pubmed/21586366?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23597047?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21586365?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22963441?dopt=AbstractPlus ]. Clinically used drugs acting on these receptors include the dinucleoside polyphosphate  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1736 , agonist of the P2Y 2  receptor subtype, approved in Japan for the management of dry eye disease [ http://www.ncbi.nlm.nih.gov/pubmed/24511227?dopt=AbstractPlus ], and the P2Y 12  receptor antagonists  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7562 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1765  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1776 , all approved as antiplatelet drugs [ http://www.ncbi.nlm.nih.gov/pubmed/23809135?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27886821?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=323 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=324 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=325 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=326 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8539 ,  http://www.uniprot.org/uniprot/P47900 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8541 ,  http://www.uniprot.org/uniprot/P41231 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8542 ,  http://www.uniprot.org/uniprot/P51582 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8543 ,  http://www.uniprot.org/uniprot/Q15077 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713  [ http://www.ncbi.nlm.nih.gov/pubmed/8564228?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713  (at rat recombinant receptors, UTP = ATP) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 \n Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734  [ http://www.ncbi.nlm.nih.gov/pubmed/11754592?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8564228?dopt=AbstractPlus ] – – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1755 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1755  [ http://www.ncbi.nlm.nih.gov/pubmed/11502873?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1710  [ http://www.ncbi.nlm.nih.gov/pubmed/9154346?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12391289?dopt=AbstractPlus ] – – – Sub/family‐selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1736  [ http://www.ncbi.nlm.nih.gov/pubmed/11206448?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1737  [ http://www.ncbi.nlm.nih.gov/pubmed/8825364?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8825364?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12183642?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1735 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1735  [ http://www.ncbi.nlm.nih.gov/pubmed/8564228?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1736  [ http://www.ncbi.nlm.nih.gov/pubmed/16475938?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1737  [ http://www.ncbi.nlm.nih.gov/pubmed/12183642?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1735 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1735  [ http://www.ncbi.nlm.nih.gov/pubmed/8825364?dopt=AbstractPlus ] – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3338  [ http://www.ncbi.nlm.nih.gov/pubmed/15345752?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8447 ‐ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8447 ) [ http://www.ncbi.nlm.nih.gov/pubmed/23751098?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1733  [ http://www.ncbi.nlm.nih.gov/pubmed/17302398?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3398  [ http://www.ncbi.nlm.nih.gov/pubmed/17125260?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5902  (EC 50  value determined using an IP 3  functional assay) [ http://www.ncbi.nlm.nih.gov/pubmed/17125260?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21417463?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17088057?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4044  [ http://www.ncbi.nlm.nih.gov/pubmed/21528910?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6199 ], ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1740  [ http://www.ncbi.nlm.nih.gov/pubmed/11754592?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5910 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5910  [ http://www.ncbi.nlm.nih.gov/pubmed/22901672?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24970757?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5903  [ http://www.ncbi.nlm.nih.gov/pubmed/20446735?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1747  [ http://www.ncbi.nlm.nih.gov/pubmed/16942026?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1728  (p K \n i  5.3) [ http://www.ncbi.nlm.nih.gov/pubmed/12391289?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1725  (p K i 5.2) [ http://www.ncbi.nlm.nih.gov/pubmed/12391289?dopt=AbstractPlus ] – – – Sub/family‐selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1739  (pIC 50  6) [ http://www.ncbi.nlm.nih.gov/pubmed/10401562?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1728  (pIC 50  4.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10401562?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9154346?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1725  (pEC 50  2–5) [ http://www.ncbi.nlm.nih.gov/pubmed/18600475?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1739  (pIC 50  4.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9647463?dopt=AbstractPlus ] – Rat \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1739  (p K \n B  6) [ http://www.ncbi.nlm.nih.gov/pubmed/26519900?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1725  (p K \n B  4) [ http://www.ncbi.nlm.nih.gov/pubmed/26519900?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1728  (p K \n B  4) [ http://www.ncbi.nlm.nih.gov/pubmed/26519900?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1724  (p K \n i  8.8–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15476670?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14584948?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1721  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/12391289?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1720  (p K \n i  7–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/8913364?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5907  (pIC 50  ∼6) [ http://www.ncbi.nlm.nih.gov/pubmed/15231488?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1738  (pEC 50  6) [ http://www.ncbi.nlm.nih.gov/pubmed/17302398?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9468  (pIC 50  4.7) [ http://www.ncbi.nlm.nih.gov/pubmed/19419204?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713  (p K \n d  6.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10779375?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1753  (pIC 50  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/15081875?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1752  (pIC 50  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/15081875?dopt=AbstractPlus ] Selective allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5808  (Negative) (p K \n i  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/25822790?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1729  (Negative) (pIC 50  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/15193995?dopt=AbstractPlus ] – – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1727 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1727  (Antagonist) (p K \n d  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/12391289?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1763 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1763  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11502873?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3408 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3408 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3408  (Agonist) – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9469  (Selective Antagonist) (pEC 50  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/24712832?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=327 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=328 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=329 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=330 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8540 ,  http://www.uniprot.org/uniprot/Q96G91 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18124 ,  http://www.uniprot.org/uniprot/Q9H244 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4537 ,  http://www.uniprot.org/uniprot/Q9BPV8 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:16442 ,  http://www.uniprot.org/uniprot/Q15391 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1713 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1783  [ http://www.ncbi.nlm.nih.gov/pubmed/19759354?dopt=AbstractPlus ] Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712  [ http://www.ncbi.nlm.nih.gov/pubmed/15199474?dopt=AbstractPlus ] – – Sub/family‐selective agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1710  [ http://www.ncbi.nlm.nih.gov/pubmed/15199474?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1755 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1755  [ http://www.ncbi.nlm.nih.gov/pubmed/11502873?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1710  [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1711 ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1755 ] – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1756  [ http://www.ncbi.nlm.nih.gov/pubmed/15893764?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10578132?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4046  [ http://www.ncbi.nlm.nih.gov/pubmed/19815812?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1714 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1714  [ http://www.ncbi.nlm.nih.gov/pubmed/10578132?dopt=AbstractPlus ] – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6203 . http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6203  [ http://www.ncbi.nlm.nih.gov/pubmed/19902968?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5908  [ http://www.ncbi.nlm.nih.gov/pubmed/21484092?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6202 ] Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1776  (pIC 50  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/12213051?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1732 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1732  (pIC 50  6) [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1764  (pIC 50  5.4) [ http://www.ncbi.nlm.nih.gov/pubmed/11502873?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1776  (pIC 50  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1732 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1732  (pIC 50  6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1764  (pIC 50  5.6) [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ] – Sub/family‐selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1728  (pIC 50  4.8–6) [ http://www.ncbi.nlm.nih.gov/pubmed/10578132?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1739  (pIC 50  5) [ http://www.ncbi.nlm.nih.gov/pubmed/10578132?dopt=AbstractPlus ] – – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1761  (p K \n i  7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/16250663?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1762  (pIC 50  6.4–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/19815812?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7360  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/24215345?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24670650?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3384  (pIC 50  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/7582510?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7858849?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1765  (p K i 7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/22984835?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1778  (pIC 50  6.2) [ http://www.ncbi.nlm.nih.gov/pubmed/15913566?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1777  (pIC 50  6) [ http://www.ncbi.nlm.nih.gov/pubmed/15913566?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5802  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/23592514?dopt=AbstractPlus ] Labelled ligands – [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1763 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1763  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11502873?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6147 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6147  (Antagonist) (p K \n d  8.3–8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/16213725?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22892887?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1774 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1774  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12815166?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9470  (Selective Antagonist) (p K i 10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/25299434?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9471  (Selective Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/26303895?dopt=AbstractPlus ]\nA series of 4‐alkyloxyimino derivatives of uridine5’‐triphosphate which could be useful for derivatization as fluorescent P2Y 2 /4/6 receptor probes has been recently synthesized [ http://www.ncbi.nlm.nih.gov/pubmed/24712832?dopt=AbstractPlus ].\nSingle nucleotide polymorphisms of the P2YR 1  gene have been associated to different platelet reactivity to ADP  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1712  [ http://www.ncbi.nlm.nih.gov/pubmed/15514209?dopt=AbstractPlus ]. Three frequent nonsynonymous P2Y 2  receptor polymorphisms have been identified, one of which was significantly more common in cystic fibrosis patients. This polymorphism is linked to increases in Ca 2+  influx in transfected cells, and might therefore play a role in disease development [ http://www.ncbi.nlm.nih.gov/pubmed/16495779?dopt=AbstractPlus ]. Although  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1734  (UTP) was also shown to be a biased agonist at P2Y 11 , this is still under debate [ http://www.ncbi.nlm.nih.gov/pubmed/25015314?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12761346?dopt=AbstractPlus ]. A group of single nucleotide polymorphisms in the P2Y 12  gene, forming the so called P2Y 12  H2 haplotype, has been associated with increased platelet responsiveness to ADP, increased risk of peripheral arterial disease and with coronary artery disease [ http://www.ncbi.nlm.nih.gov/pubmed/17803810?dopt=AbstractPlus ]. The platelet‐type bleeding disorder due to P2Y 12  receptor defects is an autosomal recessive condition characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation [ http://www.ncbi.nlm.nih.gov/pubmed/12578987?dopt=AbstractPlus ]. The P2Y 13  receptor Met‐158‐Thr polymorphism, which is in linkage disequilibrium with the P2Y 12  locus, is not associated with acute myocardial infarction, diabetes mellitus or related risk factors [ http://www.ncbi.nlm.nih.gov/pubmed/18213371?dopt=AbstractPlus ]. The P2Y 14  receptor was previously considered to exclusively bind sugar nucleotides such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1783  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1782  [ http://www.ncbi.nlm.nih.gov/pubmed/10753868?dopt=AbstractPlus ]. However, more recent evidence with several cell lines has demonstrated that  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1749  (UDP) is 5‐fold more potent than  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1783  [ http://www.ncbi.nlm.nih.gov/pubmed/19759354?dopt=AbstractPlus ]. UDP was also shown to competitively antagonise the UDP‐glucose response at the human recombinant P2Y 14  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/18252808?dopt=AbstractPlus ].\nAbbracchio MP  et al . (2006) International Union of Pharmacology LVIII: update on the P2Y G protein‐coupled nucleotide receptors: frommolecular mechanisms andpathophysiology totherapy.  Pharmacol. Rev. \n 58 : 281‐341 [ https://www.ncbi.nlm.nih.gov/pubmed/16968944?dopt=AbstractPlus ]\nJacobson KA  et al . (2015) Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.  Mol. Pharmacol. \n 88 : 220‐30 [ https://www.ncbi.nlm.nih.gov/pubmed/25837834?dopt=AbstractPlus ]\nvon Kügelgen I  et al . (2016) Pharmacology and structure of P2Y receptors.  Neuropharmacology \n 104 : 50‐61 [ https://www.ncbi.nlm.nih.gov/pubmed/26519900?dopt=AbstractPlus ]\n\nThe parathyroid hormone receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Parathyroid Hormone Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/25713287?dopt=AbstractPlus ]) are family B G protein‐coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone‐related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor‐derived peptides:  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ,  http://www.uniprot.org/uniprot/P01270 ) (84 amino acids), and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3738  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9607 ,  http://www.uniprot.org/uniprot/P12272 ) (141 amino‐acids) and related peptides (PTH‐(1‐34),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1790 ,  http://www.uniprot.org/uniprot/P12272 )). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor‐derived peptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1815  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30828 ,  http://www.uniprot.org/uniprot/Q96A98 ) (39 amino acids). [ 125 I]PTH may be used to label both PTH1 and PTH2 receptors.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=331 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=332 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9608 ,  http://www.uniprot.org/uniprot/Q03431 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9609 ,  http://www.uniprot.org/uniprot/P49190 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ,  http://www.uniprot.org/uniprot/P01270 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3738  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9607 ,  http://www.uniprot.org/uniprot/P12272 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1815  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30828 ,  http://www.uniprot.org/uniprot/Q96A98 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ,  http://www.uniprot.org/uniprot/P01270 ) ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3738  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9607 ,  http://www.uniprot.org/uniprot/P12272 ) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4448  [ http://www.ncbi.nlm.nih.gov/pubmed/8702701?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1815  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30828 ,  http://www.uniprot.org/uniprot/Q96A98 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11602681?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10854439?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1822 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7896796?dopt=AbstractPlus ] – Rat –\nThe parathyroid hormone type 1 receptor (PTHR) is the canonical GPCR for PTH and PTHrP. It is coupled to Gs and Gq and regulates the development of bone, heart, mammary glands and other tissues in response to PTHrP, and blood concentrations of calcium and phosphate ions, as well as vitamin D, in response to PTH. Another important action of the PTH/PTHR system is to stimulate bone formation when the hormone is intermittently administrated (daily injection).\nAlthough  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1785  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9606 ,  http://www.uniprot.org/uniprot/P01270 ) is an agonist at human PTH2 receptors, it fails to activate the rodent orthologues.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1815  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30828 ,  http://www.uniprot.org/uniprot/Q96A98 ) is a weak antagonist at PTH1 receptors [ http://www.ncbi.nlm.nih.gov/pubmed/11159842?dopt=AbstractPlus ].\nCheloha RW  et al . (2015) PTH receptor‐1 signalling‐mechanistic insights and therapeutic prospects.  Nat Rev Endocrinol \n 11 : 712‐24 [ https://www.ncbi.nlm.nih.gov/pubmed/26303600?dopt=AbstractPlus ]\nGardella TJ  et al . (2015) International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors‐Family B G Protein‐Coupled Receptors.  Pharmacol. Rev. \n 67 : 310‐37 [ https://www.ncbi.nlm.nih.gov/pubmed/25713287?dopt=AbstractPlus ]\nVilardaga JP  et al . (2014) Endosomal generation of cAMP in GPCR signaling.  Nat. Chem. Biol. \n 10 : 700‐6 [ https://www.ncbi.nlm.nih.gov/pubmed/25271346?dopt=AbstractPlus ]\n\nPlatelet‐activating factor ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1831 , 1‐ O ‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine) is an ether phospholipid mediator associated with platelet coagulation, but also subserves inflammatory roles. The PAF receptor ( provisional nomenclature recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) is activated by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1831  and other suggested endogenous ligands are oxidized phosphatidylcholine [ http://www.ncbi.nlm.nih.gov/pubmed/10497200?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2508  [ http://www.ncbi.nlm.nih.gov/pubmed/9038918?dopt=AbstractPlus ]. It may also be activated by bacterial lipopolysaccharide [ http://www.ncbi.nlm.nih.gov/pubmed/1333988?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=334 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9582 ,  http://www.uniprot.org/uniprot/P25105 \n Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3427 \n Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1856  (p K \n i  10.3) [ http://www.ncbi.nlm.nih.gov/pubmed/8395255?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1850  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9151941?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1852  (pIC 50  8.1–8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/15922596?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1657923?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3426  (p K \n i  7.8) [ http://www.ncbi.nlm.nih.gov/pubmed/2841449?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1860  (p K \n i  5.2–7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8798529?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8380690?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1833  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11560941?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1657923?dopt=AbstractPlus ]\nNote that a previously recommended radioligand ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1859  K d  44.6 nM) is currently unavailable.\nFoord SM  et al . (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57 : 279‐288 [ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nIshii S  et al . (2000) Platelet‐activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice.  Prog. Lipid Res. \n 39 : 41‐82 [ https://www.ncbi.nlm.nih.gov/pubmed/10729607?dopt=AbstractPlus ]\nPrescott SM  et al . (2000) Platelet‐activating factor and related lipid mediators.  Annu. Rev. Biochem. \n 69 : 419‐45 [ https://www.ncbi.nlm.nih.gov/pubmed/10966465?dopt=AbstractPlus ]\n\nProkineticin receptors, PKR 1  and PKR 2  ( provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) respond to the cysteine‐rich 81‐86 amino‐acid peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1866  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18454 ,  http://www.uniprot.org/uniprot/Q9HC23 ) (also known as endocrine glandderived vascular endothelial growth factor, mambakine) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1867  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ) (protein Bv8 homologue). An orthologue of PROK1 from black mamba ( Dendroaspis polylepi s) venom, mamba intestinal toxin 1 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1865 , [ http://www.ncbi.nlm.nih.gov/pubmed/10567694?dopt=AbstractPlus ]) is a potent, nonselective agonist at prokineticin receptors [ http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ], while  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5362 , an orthologue of PROK2 from amphibians ( Bombina sp. , [ http://www.ncbi.nlm.nih.gov/pubmed/10422759?dopt=AbstractPlus ]), is equipotent at recombinant PKR 1  and PKR 2  [ http://www.ncbi.nlm.nih.gov/pubmed/16113687?dopt=AbstractPlus ], and has high potency in macrophagechemotaxis assays, which arelost in PKR 1 null mice.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=335 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=336 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4524 ,  http://www.uniprot.org/uniprot/Q8TCW9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15836 ,  http://www.uniprot.org/uniprot/Q8NFJ6 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1867  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ,  http://www.uniprot.org/uniprot/Q9HC23 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1866  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18454 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18454 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1868 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1868  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15772293?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11886876?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12427552?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1867  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ,  http://www.uniprot.org/uniprot/Q9HC23 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1866  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18454 ,  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18454 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1868 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1868  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:18455 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15772293?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11886876?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12427552?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1865  [ http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1865  [ http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8518  [ http://www.ncbi.nlm.nih.gov/pubmed/25831128?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8517  [ http://www.ncbi.nlm.nih.gov/pubmed/25831128?dopt=AbstractPlus ] – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8522  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8522  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12054613?dopt=AbstractPlus ]\nGenetic mutations in  PROKR1  are associated with Hirschsprung's disease [ http://www.ncbi.nlm.nih.gov/pubmed/21858136?dopt=AbstractPlus ], while genetic mutations in  PROKR2  are associated with hypogonadotropic hypogonadism with anosmia [ http://www.ncbi.nlm.nih.gov/pubmed/23596439?dopt=AbstractPlus ], hypopituitarism with pituitary stalk interruption [ http://www.ncbi.nlm.nih.gov/pubmed/22466334?dopt=AbstractPlus ] and Hirschsprung's disease [ http://www.ncbi.nlm.nih.gov/pubmed/21858136?dopt=AbstractPlus ]. PKR 2  has been recently identified as a receptor for  T. cruzi  natural infection [ http://www.ncbi.nlm.nih.gov/pubmed/25324134?dopt=AbstractPlus ].\nBoulberdaa M  et al . (2011) Prokineticin receptor 1 (PKR1) signalling in cardiovascular and kidney functions.  Cardiovasc. Res. \n 92 : 191‐8 [ https://www.ncbi.nlm.nih.gov/pubmed/21856786?dopt=AbstractPlus ]\nNegri L  et al . (2018) The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell‐Dependent Angiogenesis.  Physiol. Rev. \n 98 : 1055‐1082 [ https://www.ncbi.nlm.nih.gov/pubmed/29537336?dopt=AbstractPlus ]\nNegri L  et al . (2012) Bv8/PK2 and prokineticin receptors: a druggable pronociceptive system.  Curr Opin Pharmacol \n 12 : 62‐6 [ https://www.ncbi.nlm.nih.gov/pubmed/22136937?dopt=AbstractPlus ]\nNegri L  et al . (2007) Bv8/Prokineticin proteins and their receptors.  Life Sci. \n 81 : 1103‐16 [ https://www.ncbi.nlm.nih.gov/pubmed/17881008?dopt=AbstractPlus ]\nNgan ES  et al . (2008) Prokineticin‐signaling pathway.  Int. J. Biochem. Cell Biol. \n 40 : 1679‐84 [ https://www.ncbi.nlm.nih.gov/pubmed/18440852?dopt=AbstractPlus ]\n\nThe precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) for PrRP generates 31 and 20‐amino‐acid versions.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3665  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29982 ,  http://www.uniprot.org/uniprot/P83859 ) (named after a pyroglutamylated arginine‐phenylalanine‐amide peptide) is a 43 amino acid peptide derived from  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29982  ( http://www.uniprot.org/uniprot/P83859 ) and is also known as P518 or 26RFa. RFRP is an RF amide‐related peptide [ http://www.ncbi.nlm.nih.gov/pubmed/11025660?dopt=AbstractPlus ] derived from a FMRFamide‐related peptide precursor ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ), which is cleaved to generate  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3736  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7901 ,  http://www.uniprot.org/uniprot/O15130 ), neuropeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5340  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ), neuropeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5373  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ) and neuropeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4016  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:13782 ,  http://www.uniprot.org/uniprot/Q9HCQ7 ) (neuropeptide NPVF).\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=337 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4464 ,  http://www.uniprot.org/uniprot/P49683 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1871  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1873  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) [ http://www.ncbi.nlm.nih.gov/pubmed/11030716?dopt=AbstractPlus ] Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1871  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12606605?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030716?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1873  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17945 ,  http://www.uniprot.org/uniprot/P81277 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12606605?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11030716?dopt=AbstractPlus ] Endogenous antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1504  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7955 ,  http://www.uniprot.org/uniprot/P01303 ) (p K \n i  5.4) [ http://www.ncbi.nlm.nih.gov/pubmed/15885496?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1875  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11030716?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4022  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15752583?dopt=AbstractPlus ]\nThe orphan receptor  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4523  ( http://www.uniprot.org/uniprot/Q9NYM4 ) shows sequence similarities with NPFF1, NPFF2, PrRP and QRFP receptors.\nSamson WK  et al . (2006) Prolactin releasing peptide (PrRP): an endogenous regulator of cell growth.  Peptides \n 27 : 1099‐103 [ https://www.ncbi.nlm.nih.gov/pubmed/16500730?dopt=AbstractPlus ]\nTakayanagi Y  et al . (2010) Roles of prolactin‐releasing peptide and RFamide related peptides in the control of stress and food intake.  FEBS J. \n 277 : 4998‐5005 [ https://www.ncbi.nlm.nih.gov/pubmed/21126313?dopt=AbstractPlus ]\n\nProstanoid receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Prostanoid Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/21752876?dopt=AbstractPlus ]) are activated by the endogenous ligands prostaglandins  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4483 , prostacyclin [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 . Measurement of the potency of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482  is hampered by their instability in physiological salt solution; they are often replaced by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1917  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1888 , respectively, in receptor characterization studies.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=338 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=339 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9591 ,  http://www.uniprot.org/uniprot/Q13258 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4502 ,  http://www.uniprot.org/uniprot/Q9Y5Y4 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5820  [ http://www.ncbi.nlm.nih.gov/pubmed/25542069?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22480736?dopt=AbstractPlus ] – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1878  [ http://www.ncbi.nlm.nih.gov/pubmed/7642548?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9579725?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10448933?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1879  [ http://www.ncbi.nlm.nih.gov/pubmed/9579725?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10448933?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1902  [ http://www.ncbi.nlm.nih.gov/pubmed/12721327?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12490611?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16256979?dopt=AbstractPlus ] Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8995  (p K \n d  9) [ 2072 ,  http://www.ncbi.nlm.nih.gov/pubmed/26916831?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1911  (p K \n i  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/16256979?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3356  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/17300164?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1897  (p K \n i  8.6–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/7642548?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2924081?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9579725?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8537  (p K \n i  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/21819041?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15388164?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/18178816?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1905  (pIC 50  8.9) [ http://www.ncbi.nlm.nih.gov/pubmed/17714552?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15715457?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1891  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9579725?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1891  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16418339?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12975488?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=340 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=340 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=341 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=342 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=343 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9593 ,  http://www.uniprot.org/uniprot/P34995 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9594 ,  http://www.uniprot.org/uniprot/P43116 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9595 ,  http://www.uniprot.org/uniprot/P43115 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9596 ,  http://www.uniprot.org/uniprot/P35408 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10462542?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  (EP 3 ‐III isoform) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ] – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1912  [ http://www.ncbi.nlm.nih.gov/pubmed/11999132?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5820  [ http://www.ncbi.nlm.nih.gov/pubmed/25542069?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22480736?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  [ http://www.ncbi.nlm.nih.gov/pubmed/8163486?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1936 ) (EP 3 ‐III isoform) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1912  [ http://www.ncbi.nlm.nih.gov/pubmed/27664754?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1914  [ http://www.ncbi.nlm.nih.gov/pubmed/10746663?dopt=AbstractPlus ] – Mouse \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1932  [ http://www.ncbi.nlm.nih.gov/pubmed/10746663?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10315  [ http://www.ncbi.nlm.nih.gov/pubmed/29332128?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1892  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10462542?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1919  (EP 3 ‐III isoform) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1931  [ http://www.ncbi.nlm.nih.gov/pubmed/21323896?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22342278?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3357  [ http://www.ncbi.nlm.nih.gov/pubmed/18516068?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/19584306?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1933  [ http://www.ncbi.nlm.nih.gov/pubmed/21323896?dopt=AbstractPlus ] Antagonists – – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1952  (p K \n i  7.6–8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/11408598?dopt=AbstractPlus ,  2406 ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1920  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10537280?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1924  (p K \n i  7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5817  (PF‐04418948 has weaker affinity at the EP 2 ‐receptor in guinea‐pigs) (p K \n B  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21595651?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22747912?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9283  (p K \n B  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/23914286?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5844  (EP 3 ‐III isoform (pK i =8.04 in the presence of HSA)) (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/11504634?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1943  (pIC 50  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/12538661?dopt=AbstractPlus ] – Mouse,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5822  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/19486006?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1942  (p K \n i  8.5),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1953  (p K \n i  7–7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15655509?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1916  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11999132?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1916  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1916  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1916  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10952683?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22480736?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=344 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=345 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=346 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9600 ,  http://www.uniprot.org/uniprot/P43088 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9602 ,  http://www.uniprot.org/uniprot/P43119 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11608 ,  http://www.uniprot.org/uniprot/P21731 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482 \n \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4483  ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915 \n Endogenous agonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915  [ http://www.ncbi.nlm.nih.gov/pubmed/372237?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882  [ http://www.ncbi.nlm.nih.gov/pubmed/11454473?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17704830?dopt=AbstractPlus ] – Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9875  [ http://www.ncbi.nlm.nih.gov/pubmed/25788650?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1895  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5820  [ http://www.ncbi.nlm.nih.gov/pubmed/22480736?dopt=AbstractPlus ] – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1940  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1960  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1917  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5852  [ http://www.ncbi.nlm.nih.gov/pubmed/23850788?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17545310?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1888  [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ] Antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1911  (p K \n i  8) [ http://www.ncbi.nlm.nih.gov/pubmed/1387312?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3424  (p K \n i  7.5) [ http://www.ncbi.nlm.nih.gov/pubmed/17618756?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1969  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/16331286?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4042  (p A \n 2  8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/16331286?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1976  (p K \n i  8.3–9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/8242228?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2527074?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1980  (p K \n i  8.1–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2975605?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1957  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8300593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3417  (Agonist) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1966  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7512962?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22480736?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1982  (Antagonist) (p K \n d  7.7–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/1386885?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1973  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2530338?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1985  (Antagonist) (p K \n d  7.4–8.2) [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16604093?dopt=AbstractPlus ]\nWhilst  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1917  is selective for IP receptors, it does exhibit moderate agonist potency at EP 4  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/10634944?dopt=AbstractPlus ]. Apart from IP receptors,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1895  also binds to EP 1  receptors.\nThe EP 1  agonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1912  also shows agonist activity at EP 3  and EP 4  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/21323896?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/27664754?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3379  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3331  may require de‐esterification within tissues to attain full agonist potency. There is evidence for subtypes of FP [ http://www.ncbi.nlm.nih.gov/pubmed/7830272?dopt=AbstractPlus ] and TP receptors [ http://www.ncbi.nlm.nih.gov/pubmed/8882612?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8034687?dopt=AbstractPlus ]. mRNA for the EP 3  receptor undergoes alternative splicing to produce variants which can interfere with signalling [ http://www.ncbi.nlm.nih.gov/pubmed/8940129?dopt=AbstractPlus ] or generate complex patterns of G‐protein (G i/o , G q/11 , G s  and G 12 , 13 ) coupling ( e.g.  [ http://www.ncbi.nlm.nih.gov/pubmed/7476918?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7608175?dopt=AbstractPlus ]). The number of EP 3  receptor (protein) variants are variable depending on species, with five in human, three in rat and three in mouse. Putative receptor(s) for prostamide F (which as yet lack molecular correlates) and which preferentially recognize  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5456  and its analogues ( e.g .  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1958 ) have been identified, together with moderate‐potency antagonists ( e.g. \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5455 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18700152?dopt=AbstractPlus ].\nThe free acid form of AL‐12182,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3386 , used in  in vitro  studies, has a EC 50  of 15nM which is the concentration of the compound giving half‐maximal stimulation of inositol phosphate turnover in HEK‐293 cells expressing the human FP receptor [ http://www.ncbi.nlm.nih.gov/pubmed/17076623?dopt=AbstractPlus ].\nReferences given alongside the TP receptor agonists I‐BOP [ http://www.ncbi.nlm.nih.gov/pubmed/1830308?dopt=AbstractPlus ] and STA 2  [ http://www.ncbi.nlm.nih.gov/pubmed/8242228?dopt=AbstractPlus ] use human platelets as the source of TP receptors for competition radio‐ligand binding assays to determine the indicated activity values.\nPharmacological evidence for a second IP receptor, denoted IP 2 , in the central nervous system [ http://www.ncbi.nlm.nih.gov/pubmed/8621463?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10349870?dopt=AbstractPlus ] and in the BEAS‐2B human airway epithelial cell line [ http://www.ncbi.nlm.nih.gov/pubmed/21173040?dopt=AbstractPlus ] is available. This receptor is selectively activated by 15R‐17,18,19,20‐tetranor‐16‐m‐tolylisocarbacyclin ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5864 ) and 15R‐Deoxy 17,18,19,20‐tetranor‐16m‐tolyl‐isocarbacyclin ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5865 ). However, molecular biological evidence for an IP 2  subtype is currently lacking.\nWoodward DF  et al . (2011) International union of basic and clinical pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress.  Pharmacol. Rev. \n 63 : 471‐538 [ https://www.ncbi.nlm.nih.gov/pubmed/21752876?dopt=AbstractPlus ]\n\nProteinase‐activated receptors (PARs,  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Proteinase‐activated Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/12037136?dopt=AbstractPlus ]) are unique members of the GPCR superfamily activated by proteolytic cleavage of their amino terminal exodomains. Agonist proteinase‐induced hydrolysis unmasks a tethered ligand (TL) at the exposed amino terminus, which acts intramolecularly at the binding site in the body of the receptor to effect transmembrane signalling. TL sequences at human PAR1‐4 are  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5361 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3740 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5360  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3739 , respectively. With the exception of PAR3, synthetic peptides with these sequences (as carboxyl terminal amides) are able to act as agonists at their respective receptors. Several proteinases, including neutrophil elastase, cathepsin G and chymotrypsin can have inhibitory effects at PAR1 and PAR2 such that they cleave the exodomain of the receptor without inducing activation of Gαq‐coupled calcium signalling, thereby preventing activation by activating proteinases but not by agonist peptides. Neutrophil elastase (NE) cleavage of PAR1 and PAR2 can however activate MAP kinase signaling by exposing a TL that is different from the one revealed by trypsin [ http://www.ncbi.nlm.nih.gov/pubmed/22212680?dopt=AbstractPlus ]. PAR2 ectivation by NE regulates inflammation and pain responses [ http://www.ncbi.nlm.nih.gov/pubmed/26140667?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25878251?dopt=AbstractPlus ] and triggers mucin secretion from airway epithelial cells [ http://www.ncbi.nlm.nih.gov/pubmed/23392769?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=347 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=348 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=349 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=350 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3537 ,  http://www.uniprot.org/uniprot/P25116 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3538 ,  http://www.uniprot.org/uniprot/P55085 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3539 ,  http://www.uniprot.org/uniprot/O00254 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3540 ,  http://www.uniprot.org/uniprot/Q96RI0 \n Agonist proteases \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4453  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ), activated  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4473  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9451 ,  http://www.uniprot.org/uniprot/P04070 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6655  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7155 ,  http://www.uniprot.org/uniprot/P45452 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6656  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7159 ,  http://www.uniprot.org/uniprot/P45452 ) [ http://www.ncbi.nlm.nih.gov/pubmed/23086754?dopt=AbstractPlus ] Trypsin, tryptase, TF/VIIa, Xa;  http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2358 \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2353  [ http://www.ncbi.nlm.nih.gov/pubmed/30012612?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21576245?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4453  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4453  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ), trypsin,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3570  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2532 ,  http://www.uniprot.org/uniprot/P08311 ) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9255 \n – – – Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3742  [ http://www.ncbi.nlm.nih.gov/pubmed/11877318?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9455  [ http://www.ncbi.nlm.nih.gov/pubmed/26819675?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6657  [ http://www.ncbi.nlm.nih.gov/pubmed/20873792?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3851  [ http://www.ncbi.nlm.nih.gov/pubmed/14976230?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3740  [ http://www.ncbi.nlm.nih.gov/pubmed/18179608?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3741  [ http://www.ncbi.nlm.nih.gov/pubmed/18179608?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4061 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3883 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3739 \n Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4047  (p K \n i  8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/18447380?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4048  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/21300059?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3525  (pIC 50  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/10535908?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10268  (pIC 50  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/29263243?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9585  (p K \n d  6.5) [ http://www.ncbi.nlm.nih.gov/pubmed/28445455?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6658  (pIC 50  5.7) [ http://www.ncbi.nlm.nih.gov/pubmed/21806599?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6659  [ http://www.ncbi.nlm.nih.gov/pubmed/21536878?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10269  (p K \n d  10) [ http://www.ncbi.nlm.nih.gov/pubmed/28053157?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9458  (pIC 50  6.9) [ http://www.ncbi.nlm.nih.gov/pubmed/25176330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9459  (pIC 50  6.8) [ http://www.ncbi.nlm.nih.gov/pubmed/25176330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10270  [ http://www.ncbi.nlm.nih.gov/pubmed/12357249?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10271  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/28126849?dopt=AbstractPlus ] Allosteric modulators – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9560  (Negative) (pIC 50  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/28445455?dopt=AbstractPlus ] – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3823  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9203642?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4050  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/18477767?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4049  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/18477767?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6660  (Selective Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15765104?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3914  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10411588?dopt=AbstractPlus ] – – Comments \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3742  is selective relative to the PAR 2  receptor [ http://www.ncbi.nlm.nih.gov/pubmed/8663335?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9862790?dopt=AbstractPlus ]. 2‐Furoyl‐LIGRLO‐NH 2  activity was measured via calcium mobilisation in HEK 293 cells which constitutively coexpress human PAR 1  and PAR 2 . – –\nEndogenous serine proteases (EC 3.4.21.) active at the proteinase‐activated receptors include:  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4453  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ), generated by the action of Factor X ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3528 ,  http://www.uniprot.org/uniprot/P00742 ) on liver‐derived prothrombin ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ); trypsin, generated by the action of enterokinase ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9490 ,  http://www.uniprot.org/uniprot/P98073 ) on pancreatic‐derived trypsinogen ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9475 ,  http://www.uniprot.org/uniprot/P07477 ); tryptase, a family of enzymes (α/β1  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12019 ,  http://www.uniprot.org/uniprot/Q15661 ; γ1  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14134 ,  http://www.uniprot.org/uniprot/Q9NRR2 \n δ 1  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14118 ,  http://www.uniprot.org/uniprot/Q9BZJ3 ) secreted from mast cells; cathepsin G ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:2532 ,  http://www.uniprot.org/uniprot/P08311 ) generated from leukocytes; liver‐derived protein C ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:9451 ,  http://www.uniprot.org/uniprot/P04070 ) generated in plasma by  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4453  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:3535 ,  http://www.uniprot.org/uniprot/P00734 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6655  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:7155 ,  http://www.uniprot.org/uniprot/P45452 ).\nAdams MN  et al.  (2011) Structure, function and pathophysiology of protease activated receptors.  Pharmacol. Ther. \n 130:  248‐82  https://www.ncbi.nlm.nih.gov/pubmed/21277892?dopt=AbstractPlus\nCanto I  et al.  (2012) Allosteric modulation of protease‐activated receptor signaling.  Mini Rev Med Chem \n 12:  804‐11  https://www.ncbi.nlm.nih.gov/pubmed/22681248?dopt=AbstractPlus\nGarcía PS  et al.  (2010) The role of thrombin and protease‐activated receptors in pain mechanisms.  Thromb. Haemost. \n 103:  1145‐51  https://www.ncbi.nlm.nih.gov/pubmed/20431855?dopt=AbstractPlus\nHollenberg MD  et al.  (2002) International Union of Pharmacology. XXVIII. Proteinase‐activated receptors.  Pharmacol. Rev. \n 54:  203‐17  https://www.ncbi.nlm.nih.gov/pubmed/12037136?dopt=AbstractPlus\nRamachandran R  et al.  (2012) Targeting proteinase‐activated receptors: therapeutic potential and challenges.  Nat Rev Drug Discov \n 11:  69‐86  https://www.ncbi.nlm.nih.gov/pubmed/22212680?dopt=AbstractPlus\nSoh UJ  et al.  (2010) Signal transduction by protease‐activated receptors.  Br. J. Pharmacol. \n 160:  191‐203  https://www.ncbi.nlm.nih.gov/pubmed/20423334?dopt=AbstractPlus\n\nThe human gene encoding the QRFP receptor ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the QRFP receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/28613414?dopt=AbstractPlus ]; QRFPR, formerly known as the Peptide P518 receptor), previously designated as an orphan GPCR receptor was identified in 2001 by Lee  et al.  from a hypothalamus cDNA library [ http://www.ncbi.nlm.nih.gov/pubmed/11574155?dopt=AbstractPlus ]. However, the reported cDNA ( AF411117 ) is a chimera with bases 1‐127 derived from chromosome 1 and bases 155‐1368 derived from chromosome 4. When corrected, QRFPR (also referred to as SP9155 or AQ27) encodes a 431 amino acid protein that shares sequence similarities in the transmembrane spanning regions with other peptide receptors. These include neuropeptide FF2 (38%), neuropeptide Y 2  (37%) and galanin Gal 1  (35%) receptors.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=333 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:15565 ,  http://www.uniprot.org/uniprot/Q96P65 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5895  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:29982 ) [ http://www.ncbi.nlm.nih.gov/pubmed/14657341?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12714592?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10252  [ http://www.ncbi.nlm.nih.gov/pubmed/30358997?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9442  [ http://www.ncbi.nlm.nih.gov/pubmed/22800498?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9443  (pIC 50  7.3) [ http://www.ncbi.nlm.nih.gov/pubmed/24937104?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25875054?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3803 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12960173?dopt=AbstractPlus ,  1164 ,  http://www.ncbi.nlm.nih.gov/pubmed/16648250?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10253 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/17534937?dopt=AbstractPlus ]\nThe orphan receptor  http://www.guidetopharmacology.org/GRAC/  ( http://www.uniprot.org/uniprot/9NYM4 ) shows sequence similarities with the QRFP receptor, as well as with the NPFF1, NPFF2, and PrRP receptors.\nChartrel N  et al.  (2011) The RFamide neuropeptide 26RFa and its role in the control of neuroendocrine functions.  Front Neuroendocrinol \n 32 : 387‐97  https://www.ncbi.nlm.nih.gov/pubmed/21530572?dopt=AbstractPlus\nFukusumi S  et al.  (2006) Recent advances in mammalian RFamide peptides: the discovery and functional analyses of PrRP, RFRPs and QRFP.  Peptides \n 27:  1073‐86  https://www.ncbi.nlm.nih.gov/pubmed/16500002?dopt=AbstractPlus\nLeprince J  et al.  (2017) The Arg‐Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24.  Br. J. Pharmacol. \n 174 : 3573‐3607  https://www.ncbi.nlm.nih.gov/pubmed/28613414?dopt=AbstractPlus\n\nRelaxin family peptide receptors (RXFP,  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Relaxin family peptide receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/16507880?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25761609?dopt=AbstractPlus ]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin:  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1988  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10026 ,  http://www.uniprot.org/uniprot/P04808 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) (also known as INSL7), insulin‐like peptide 3 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1995  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6086 ,  http://www.uniprot.org/uniprot/P51460 )) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ). Species homologues of relaxin have distinct pharmacology and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [ http://www.ncbi.nlm.nih.gov/pubmed/15956680?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [ http://www.ncbi.nlm.nih.gov/pubmed/15956681?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) is the ligand for RXFP4 but is a weak antagonist of RXFP3.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1995  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6086 ,  http://www.uniprot.org/uniprot/P51460 ) have multiple complex binding interactions with RXFP1 [ http://www.ncbi.nlm.nih.gov/pubmed/27088579?dopt=AbstractPlus ] and RXFP2 [ http://www.ncbi.nlm.nih.gov/pubmed/30594862?dopt=AbstractPlus ] which direct the N‐terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct receptor signaling [ http://www.ncbi.nlm.nih.gov/pubmed/16963451?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) interact with their receptors using distinct residues in their B‐chains for binding, and activation, respectively [ http://www.ncbi.nlm.nih.gov/pubmed/28274616?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30131340?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=351 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=352 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=353 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=354 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:19718 ,  http://www.uniprot.org/uniprot/Q9HBX9 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17318 ,  http://www.uniprot.org/uniprot/Q8WXD0 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:24883 ,  http://www.uniprot.org/uniprot/Q9NSD7 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14666 ,  http://www.uniprot.org/uniprot/Q8TDU9 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1988  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10026 ,  http://www.uniprot.org/uniprot/P04808 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12506116?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1995  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6086 ,  http://www.uniprot.org/uniprot/P51460 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12114498?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12506116?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1997  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) [ http://www.ncbi.nlm.nih.gov/pubmed/14522968?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1997  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15465925?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/14522967?dopt=AbstractPlus ] Endogenous antagonists – – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) (p K \n i  7) [ http://www.ncbi.nlm.nih.gov/pubmed/18582868?dopt=AbstractPlus ] – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4371  (pEC 50  5.7–6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/20043231?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24812057?dopt=AbstractPlus ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3907  (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/17606621?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3907  (pIC 50  8–8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17606621?dopt=AbstractPlus ] Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8329  (p K \n i  9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/18434306?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8330  (p K \n i  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/18434306?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8331  (p K \n i  8.6) [ http://www.ncbi.nlm.nih.gov/pubmed/20570702?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4372  (p K i 8.5) [ http://www.ncbi.nlm.nih.gov/pubmed/20560146?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8332  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/20570702?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8333  (p K i 6.7) [ http://www.ncbi.nlm.nih.gov/pubmed/17120268?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3885  (p K i 5.1) [ http://www.ncbi.nlm.nih.gov/pubmed/16547350?dopt=AbstractPlus ], ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3754  [ http://www.ncbi.nlm.nih.gov/pubmed/15708846?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8326  (p K \n i  7.6) [ http://www.ncbi.nlm.nih.gov/pubmed/22257012?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4373  (p K \n i  7.4) [ http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8326  (pIC 50  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/22257012?dopt=AbstractPlus ] Allosteric modulators \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8322  (Agonist) (pEC 50  7) [ http://www.ncbi.nlm.nih.gov/pubmed/23905199?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23764525?dopt=AbstractPlus ] – – – Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1991  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15649866?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12506116?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3874  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/22425984?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5398  (Agonist) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1996  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/16051677?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1991  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15649866?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12506116?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1999 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/14522968?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3789  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15465925?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4374  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1999 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/14522967?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3789  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/15465925?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6522  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21866895?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4374  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4375  (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ] Comments – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3875  is a fluorescent ligand for this receptor ( K \n d =1nM) [ http://www.ncbi.nlm.nih.gov/pubmed/18529069?dopt=AbstractPlus ]. – –\nhttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) is the cognate peptide ligand for RXFP1 and is in extended Phase III clinical trials for the treatment of acute heart failure [ http://www.ncbi.nlm.nih.gov/pubmed/23273292?dopt=AbstractPlus ]. Relaxin has vasodilatory, anti‐fibrotic, angiogenic, anti‐apoptotic and anti‐inflammatory effects. A small molecule allosteric agonists  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8322  has been developed [ http://www.ncbi.nlm.nih.gov/pubmed/18854305?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23764525?dopt=AbstractPlus ], and a relaxin B‐chain mimetic peptide B7‐33 has been developed which that has cell specific signaling properties [ http://www.ncbi.nlm.nih.gov/pubmed/30155023?dopt=AbstractPlus ]. The antifibrotic actions of relaxin are dependent on the angiotensin receptor AT 2  [ http://www.ncbi.nlm.nih.gov/pubmed/24429402?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1995  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6086 ,  http://www.uniprot.org/uniprot/P51460 ) is the cognate peptide for RXFP2 and is a circulating hormone that in males is essential for testicular descent  in utero  [ http://www.ncbi.nlm.nih.gov/pubmed/10391220?dopt=AbstractPlus ] and in females has important roles in ovarian follicle function [ http://www.ncbi.nlm.nih.gov/pubmed/30204868?dopt=AbstractPlus ]. In adults, INSL3 has potential roles in testicular function [ http://www.ncbi.nlm.nih.gov/pubmed/20952422?dopt=AbstractPlus ] and the musculoskeletal system [ http://www.ncbi.nlm.nih.gov/pubmed/30625346?dopt=AbstractPlus ]. RXFP2 is also present in brain, associated with cortico‐thalamic motor circuits [ http://www.ncbi.nlm.nih.gov/pubmed/18706979?dopt=AbstractPlus ]. cAMP elevation is the major signalling pathway for both RXFP1 and RXFP2 [ http://www.ncbi.nlm.nih.gov/pubmed/10935549?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11809971?dopt=AbstractPlus ], but RXFP1 also activates MAP kinases, nitric oxide signalling, and tyrosine kinase phosphorylation; and relaxin can interact with glucocorticoid receptors [ http://www.ncbi.nlm.nih.gov/pubmed/17293890?dopt=AbstractPlus ]. Receptor expression profiles suggest that RXFP3 is a brain neuropeptide receptor and RXFP4 a gut hormone receptor. The brain relaxin‐3/RXFP3 system modulates feeding [ http://www.ncbi.nlm.nih.gov/pubmed/23135160?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22854307?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21384867?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22257012?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/21899720?dopt=AbstractPlus ]  via  effects in hypothalamus [ http://www.ncbi.nlm.nih.gov/pubmed/28864207?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23135160?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28098344?dopt=AbstractPlus ], anxiety [ http://www.ncbi.nlm.nih.gov/pubmed/24297931?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/26057358?dopt=AbstractPlus ], reward and motivated, goal‐directed behaviours [ http://www.ncbi.nlm.nih.gov/pubmed/25257104?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/24297931?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25849482?dopt=AbstractPlus ], and spatial and social memory [ http://www.ncbi.nlm.nih.gov/pubmed/30368554?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/28100033?dopt=AbstractPlus ]. Of the other relaxin peptides,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 )is anagonist atRXFP3 and RXFP4 whereas http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) is an agonist at RXFP4 and a weak antagonist at RXFP3.  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2000  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:6088 ,  http://www.uniprot.org/uniprot/Q9Y5Q6 ) is secreted from enteroendocrine L cells and the INSL5/RXFP4 system affects food intake [ http://www.ncbi.nlm.nih.gov/pubmed/25028498?dopt=AbstractPlus ] and glucose homeostasis [ http://www.ncbi.nlm.nih.gov/pubmed/25514935?dopt=AbstractPlus ]. RXFP3 and RXFP4 couple to G i/o  and inhibit adenylyl cyclase [ http://www.ncbi.nlm.nih.gov/pubmed/14522968?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20159943?dopt=AbstractPlus ], and also cause Erk1/2 phosphorylation [ http://www.ncbi.nlm.nih.gov/pubmed/20159943?dopt=AbstractPlus ]. RXFP4 also causes phosphorylation of p38MAPK, Akt and S6RP [ http://www.ncbi.nlm.nih.gov/pubmed/27243554?dopt=AbstractPlus ] and GLP‐1 secretion  in vitro  [ http://www.ncbi.nlm.nih.gov/pubmed/29535183?dopt=AbstractPlus ]. There is evidence that at RXFP3,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1989  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10027 ,  http://www.uniprot.org/uniprot/P04090 ) is a biased ligand compared to the cognate ligand  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1990  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17135 ,  http://www.uniprot.org/uniprot/Q8WXF3 ) [ http://www.ncbi.nlm.nih.gov/pubmed/20159943?dopt=AbstractPlus ].\nBathgate RA  et al.  (2013) Relaxin family peptides and their receptors.  Physiol. Rev. \n 93:  405‐80  https://www.ncbi.nlm.nih.gov/pubmed/23303914?dopt=AbstractPlus\nDu XJ  et al.  (2010) Cardiovascular effects of relaxin: from basic science to clinical therapy.  Nat Rev Cardiol \n 7:  48‐58  https://www.ncbi.nlm.nih.gov/pubmed/19935741?dopt=AbstractPlus\nHalls ML  et al.  (2015) International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1‐4, the receptors for relaxin family peptides.  Pharmacol. Rev. \n 67:  389‐440  https://www.ncbi.nlm.nih.gov/pubmed/25761609?dopt=AbstractPlus\nIvell R  etal.  (2011) Relaxin family peptides in the male reproductive system‐a critical appraisal.  Mol. Hum. Reprod. \n 17:  71‐84  https://www.ncbi.nlm.nih.gov/pubmed/20952422?dopt=AbstractPlus\n\nSomatostatin (somatotropin release inhibiting factor) is an abundant neuropeptide, which acts on five subtypes of somatostatin receptor (SST 1 ‐SST 5 ;  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Somatostatin Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/30232095?dopt=AbstractPlus ]). Activation of these receptors produces a wide range of physiological effects throughout the body including the inhibition of secretion of many hormones. Endogenous ligands for these receptors are somatostatin‐14 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2019  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11329 ,  http://www.uniprot.org/uniprot/P61278 )) and somatostatin‐28 ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2020  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11329 ,  http://www.uniprot.org/uniprot/P61278 )).  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2007  {Mouse, Rat} has also been suggested to be an endogenous ligand for somatostatin receptors [ http://www.ncbi.nlm.nih.gov/pubmed/8622767?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=355 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=356 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=357 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=358 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=359 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11330 ,  http://www.uniprot.org/uniprot/P30872 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11331 ,  http://www.uniprot.org/uniprot/P30874 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11332 ,  http://www.uniprot.org/uniprot/P32745 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11333 ,  http://www.uniprot.org/uniprot/P31391 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11334 ,  http://www.uniprot.org/uniprot/P35346 \n Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2018  [ http://www.ncbi.nlm.nih.gov/pubmed/15477717?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2018  [ http://www.ncbi.nlm.nih.gov/pubmed/15477717?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8487  [ http://www.ncbi.nlm.nih.gov/pubmed/11145612?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2018  [ http://www.ncbi.nlm.nih.gov/pubmed/15477717?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3513  [ http://www.ncbi.nlm.nih.gov/pubmed/9822540?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8487  [ http://www.ncbi.nlm.nih.gov/pubmed/11145612?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2018  [ http://www.ncbi.nlm.nih.gov/pubmed/15477717?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8487  [ http://www.ncbi.nlm.nih.gov/pubmed/11145612?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2015  [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2010  [ http://www.ncbi.nlm.nih.gov/pubmed/15658864?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2046  [ http://www.ncbi.nlm.nih.gov/pubmed/9724791?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2033  [ http://www.ncbi.nlm.nih.gov/pubmed/8646408?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2050  [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2055  [ http://www.ncbi.nlm.nih.gov/pubmed/8769372?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7988476?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9652348?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10598788?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9650799?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9724791?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2031  [ http://www.ncbi.nlm.nih.gov/pubmed/8769372?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7988476?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9652348?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10598788?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9650799?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2073  [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2082  [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10115  [ http://www.ncbi.nlm.nih.gov/pubmed/15333679?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2004  [ http://www.ncbi.nlm.nih.gov/pubmed/9600011?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9652348?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10598788?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9650799?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2016  [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2030  (p K \n d  8–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15135911?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10113  [ http://www.ncbi.nlm.nih.gov/pubmed/18543899?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10114  (pIC 50  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/24900499?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2076  (p K \n i  7.9) [ 917 ] – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10116  (p K \n i  9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/28938487?dopt=AbstractPlus ]\n[ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2060 , [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2023 , [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2022  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2024  may be used to label somatostatin receptors nonselectively. A number of nonpeptide subtype‐selective agonists have been synthesised [ http://www.ncbi.nlm.nih.gov/pubmed/9784130?dopt=AbstractPlus ]. Octreotide and lanreotide are being used in the treatment of SST 2 ‐expressing neuroendocrine tumors and pasireotide for SST 5 ‐expressing neuroendocrine tumors. A novel peptide somatostatin analogue, veldoreotide (COR‐005), has affinity for SST 2 , SST 4  and SST 5  receptors and is a potent inhibitor of GH secretion [ http://www.ncbi.nlm.nih.gov/pubmed/22065857?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15636423?dopt=AbstractPlus ].\nColao A  et al.  (2011) Resistance to somatostatin analogs in acromegaly.  Endocr. Rev. \n 32:  247‐71  https://www.ncbi.nlm.nih.gov/pubmed/21123741?dopt=AbstractPlus\nGünther T  et al.  (2018) International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.  Pharmacol. Rev. \n 70:  763‐835  https://www.ncbi.nlm.nih.gov/pubmed/30232095?dopt=AbstractPlus\nHoyer D  et al.  (2000) Somatostatin receptors.  In The IUPHAR Compendium of Receptor Characterization and Classification, 2nd edn.  Edited by Watson SP, Girdlestone D: IUPHAR Media: 354‐364\nSchulz S  et al.  (2014) Fine‐tuning somatostatin receptor signalling by agonist‐selective phosphorylation and dephosphorylation: IUPHAR Review 5.  Br. J. Pharmacol. \n 171:  1591‐9  https://www.ncbi.nlm.nih.gov/pubmed/24328848?dopt=AbstractPlus\nWeckbecker G  et al.  (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects.  Nat Rev Drug Discov \n 2:  999‐1017  https://www.ncbi.nlm.nih.gov/pubmed/14654798?dopt=AbstractPlus\n\nNomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus ]. The Succinate receptor has been identified as being activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids such as maleate in 2004. Since its pairing with its endogenous ligand, the receptor has been the focus of intensive research and its role has been evidenced in various (patho)physiological processes such as regulation of renin production, retinal angiogenesis, inflammation or immune response.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=166 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4542 ,  http://www.uniprot.org/uniprot/Q9BXA5 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3637  [ http://www.ncbi.nlm.nih.gov/pubmed/15141213?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/23396314?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9630  [ http://www.ncbi.nlm.nih.gov/pubmed/28160606?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10296  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/29968758?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9631  [ http://www.ncbi.nlm.nih.gov/pubmed/29157600?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10294  (Partial agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/29157600?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9631  [ http://www.ncbi.nlm.nih.gov/pubmed/28160606?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9630  [ http://www.ncbi.nlm.nih.gov/pubmed/26386312?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9630  [ http://www.ncbi.nlm.nih.gov/pubmed/15141213?dopt=AbstractPlus ]\nIn humans, there is the possibility of two open‐reading frames (ORFs) for  SUCNR1 , one giving a protein of 330 amino acids (AA) and the other one 334‐AA. Wittenberger  et al.  [ http://www.ncbi.nlm.nih.gov/pubmed/11273702?dopt=AbstractPlus ] noted that the 330‐AA protein was more likely to be expressed given the Kozak sequence surrounding the second ATG. Some databases report  SUCNR1  as being 334‐AA long.\nAriza AC  et al.  (2012) The succinate receptor as a novel therapeutic target for oxidative and metabolic stress‐related conditions.  Front Endocrinol (Lausanne) \n 3 :22 [ https://www.ncbi.nlm.nih.gov/pubmed/22649411?dopt=AbstractPlus ]\nde Castro Fonseca M  et al.  (2016) GPR91: expanding the frontiers of Krebs cycle intermediates.  Cell Commun. Signal \n 14 :3[ https://www.ncbi.nlm.nih.gov/pubmed/26759054?dopt=AbstractPlus ]\nGilissen J  et al.  (2016) Insight into SUCNR1 (GPR91) structure and function.  Pharmacol. Ther. \n 159:  56‐65[ https://www.ncbi.nlm.nih.gov/pubmed/26808164?dopt=AbstractPlus ]\nGrimolizzi F  et al.  (2018) Multiple faces of succinate beyond metabolism in blood.  Haematologica \n 103:  1586‐1592[ https://www.ncbi.nlm.nih.gov/pubmed/29954939?dopt=AbstractPlus ]\n\nTachykinin receptors ( provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2098  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) (SP),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2089 ) (NKA; previously known as substance K, neurokinin α, neuromedin L),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2090  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11521 ,  http://www.uniprot.org/uniprot/Q9UHF0 ) (NKB; previously known as neurokinin β, neuromedin K),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2091  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3667  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ) (N‐terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe‐x‐Gly‐LeuMet. Marked species differences in  in vitro  pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3490  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7623  were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=360 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=361 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=362 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11526 ,  http://www.uniprot.org/uniprot/P25103 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11527 ,  http://www.uniprot.org/uniprot/P21452 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11528 ,  http://www.uniprot.org/uniprot/P29371 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2098  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2089 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2090  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11521 ,  http://www.uniprot.org/uniprot/Q9UHF0 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2089  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2090  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11521 ,  http://www.uniprot.org/uniprot/Q9UHF0 )  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2098 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2090  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11521 ,  http://www.uniprot.org/uniprot/Q9UHF0 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2089  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2098 ) Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2101  [ http://www.ncbi.nlm.nih.gov/pubmed/8702757?dopt=AbstractPlus ] – – Selective agonists [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3850  [ http://www.ncbi.nlm.nih.gov/pubmed/8702757?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2095  [ http://www.ncbi.nlm.nih.gov/pubmed/11786503?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8985159?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3849  [ http://www.ncbi.nlm.nih.gov/pubmed/9243521?dopt=AbstractPlus ] – Rat [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3843 ) [ http://www.ncbi.nlm.nih.gov/pubmed/9718274?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3881  [ http://www.ncbi.nlm.nih.gov/pubmed/1331460?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2112 ) [ http://www.ncbi.nlm.nih.gov/pubmed/7682062?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2113  [ http://www.ncbi.nlm.nih.gov/pubmed/11226387?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2127 ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8702757?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10349  (pIC 50  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/11708932?dopt=AbstractPlus ] – – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3490  (p K \n i  10.1) [ http://www.ncbi.nlm.nih.gov/pubmed/10737756?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9804700?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2102  (p K i 9.3–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12206858?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3522  (pIC 50  7.7) [ http://www.ncbi.nlm.nih.gov/pubmed/1281470?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3882  (p K \n i  9.8) [ http://www.ncbi.nlm.nih.gov/pubmed/8027981?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2111  (p K \n i  9.4–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12206858?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7682062?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2115  (p K \n d  7.8–9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/7713168?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7562907?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3901  (p K \n i  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/11063600?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2123  (p K i 8.5–8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9484857?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16979621?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2110  (p K \n i  8.4–9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/12206858?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9042606?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7476898?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7830490?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11757797?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7616392?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11226387?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8702757?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2132  (p K \n i  7.4–9) [ http://www.ncbi.nlm.nih.gov/pubmed/15265501?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8691422?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11226387?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9190866?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2125  (pIC 50  7.8–7.9) [ http://www.ncbi.nlm.nih.gov/pubmed/8648606?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8702757?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3471  (Antagonist) (p K \n d  9.5) [ http://www.ncbi.nlm.nih.gov/pubmed/8287060?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3769  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1705465?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3835 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2410593?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3805 ) (Agonist), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3473  (Antagonist) [ 367 ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3481  (Antagonist) (p K \n d  9.7) [ http://www.ncbi.nlm.nih.gov/pubmed/7719707?dopt=AbstractPlus ] – Rat, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3795 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10455255?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3822  (Antagonist) (p K \n d  9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/8210508?dopt=AbstractPlus ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3480  (Antagonist) (p K \n d  9.9), [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3834  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/1694464?dopt=AbstractPlus ] – Guinea pig, [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3763  (Agonist)\nThe NK 1  receptor has also been described to couple to G proteins other than G q/11  [ http://www.ncbi.nlm.nih.gov/pubmed/9654151?dopt=AbstractPlus ]. The crystal structure of the human NK 1  receptor in complex with antagonists has been determined [ http://www.ncbi.nlm.nih.gov/pubmed/30604743?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/30538204?dopt=AbstractPlus ]. The hexapeptide agonist septide appears to bind to an overlapping but non‐identical site to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2098  ( https://www.genenames.org/data/gene‐symbol‐report/%23!/hgnc_id/HGNC:11517 ,  http://www.uniprot.org/uniprot/P20366 ) on the NK 1  receptor. There are additional subtypes of tachykinin receptor;an orphan receptor (Swis‐sProt  http://www.ncbi.nlm.nih.gov/protein/266702/ ) with structural similarities to the NK 3  receptor was found to respond to NKB when expressed in  Xenopus  oocytes or Chinese hamster ovary cells [ http://www.ncbi.nlm.nih.gov/pubmed/8947459?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8990205?dopt=AbstractPlus ].\nDouglas SD  et al.  (2011) Neurokinin‐1 receptor: functional significance in the immune system in reference to selected infections and inflammation.  Ann. N. Y. Acad. Sci. \n 1217:  83‐95[ https://www.ncbi.nlm.nih.gov/pubmed/21091716?dopt=AbstractPlus ]\nFoord SM  et al.  (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57:  279‐288[ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nJones S  et al.  (2008) The neurokinin 1 receptor: a potential new target for anti‐platelet therapy?  Curr Opin Pharmacol \n 8:  114‐9[ https://www.ncbi.nlm.nih.gov/pubmed/18296119?dopt=AbstractPlus ]\nSteinhoff MS  et al.  (2014) Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.  Physiol. Rev. \n 94:  265‐301[ https://www.ncbi.nlm.nih.gov/pubmed/24382888?dopt=AbstractPlus ]\nYin J  et al.  (2018) Crystal structure of the human NK_1 tachykinin receptor.  Proc. Natl. Acad. Sci. U.S.A. \n 115:  13264‐13269[ https://www.ncbi.nlm.nih.gov/pubmed/30538204?dopt=AbstractPlus ]\n\nThyrotropin‐releasing hormone (TRH) receptors ( provisional nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous tripeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2139  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12298 ,  http://www.uniprot.org/uniprot/P20396 ) (pGlu‐His‐ProNH2).  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2139  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12298 ,  http://www.uniprot.org/uniprot/P20396 ) and TRH analogues fail to distinguish TRH 1  and TRH 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/12683933?dopt=AbstractPlus ]. [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3836 ) is able to label both TRH 1  and TRH 2  receptors with K d  values of 13 and 9 nM respectively. Synthesis and biology of ring‐modified L‐Histidine containing TRH analogues has been reported [ http://www.ncbi.nlm.nih.gov/pubmed/26854379?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=363 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=754 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12299 ,  http://www.uniprot.org/uniprot/P34981 \n – Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3364  (p K \n i  5.2) [ http://www.ncbi.nlm.nih.gov/pubmed/2566295?dopt=AbstractPlus ] – Rat – Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3342  (p K \n i  5.5) [ http://www.ncbi.nlm.nih.gov/pubmed/2566295?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3370  (p K \n i  4.8) [ http://www.ncbi.nlm.nih.gov/pubmed/2566295?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3370  (p K \n i  4.7) [ http://www.ncbi.nlm.nih.gov/pubmed/2175902?dopt=AbstractPlus ] – Mouse – Comments – A class A G protein‐coupled receptor: not present in man\nBílek R  etal.  (2011) TRH‐like peptides.  Physiol Res \n 60:  207‐15[ https://www.ncbi.nlm.nih.gov/pubmed/21114375?dopt=AbstractPlus ]\nFoord SM  et al.  (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57:  279‐288[ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nNillni EA. (2010) Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs.  Front Neuroendocrinol \n 31:  134‐56[ https://www.ncbi.nlm.nih.gov/pubmed/20074584?dopt=AbstractPlus ]\n\nTrace amine‐associated receptors were discovered from a search for novel 5‐HT receptors [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ], where 15 mammalian orthologues were identified and divided into two families. The TA 1  receptor ( nomenclature as agreed by the \n NC‐IUPHAR Subcommittee for the Trace amine receptor  [ http://www.ncbi.nlm.nih.gov/pubmed/19325074?dopt=AbstractPlus ] ) has affinity for the endogenous trace amines  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2150 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2144  and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2149  in addition to the classical amine  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ]. Emerging evidence suggests that TA 1  is a modulator of monoaminergic activity in the brain [ http://www.ncbi.nlm.nih.gov/pubmed/19482011?dopt=AbstractPlus ] with TA 1  and dopamine D 2  receptors shown to form constitutive heterodimers when co‐expressed [ http://www.ncbi.nlm.nih.gov/pubmed/21670104?dopt=AbstractPlus ]. In addition to trace amines, receptors can be activated by amphetamine‐like psychostimulants, and endogenous thyronamines.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=364 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:17734 ,  http://www.uniprot.org/uniprot/Q96RJ0 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2150  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2144  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2149  =  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=940  [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ] Agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5862  [ http://www.ncbi.nlm.nih.gov/pubmed/21525407?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5457  (Inverse agonist) (pIC 50  5.1) [ http://www.ncbi.nlm.nih.gov/pubmed/19892733?dopt=AbstractPlus ] Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2148  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ]\nIn addition to TA 1 , in man there are up to 5 functional TAAR genes (TAAR2,5,6,8,9). See [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ] for detailed discussion. The product of the gene TAAR2 (also known as GPR58) appears to respond to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2144  >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2150  and to couple through Gs [ http://www.ncbi.nlm.nih.gov/pubmed/11459929?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_168 , in some individuals, and  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_169  are pseudogenes in man, although functional in rodents. The signalling characteristics and pharmacology of  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_170  (PNR, Putative Neurotransmitter Receptor:  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30236 ,  http://www.uniprot.org/uniprot/O14804 ),  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_171 \n http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_171  (Trace amine receptor 4, TaR‐4:  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20978 ,  http://www.uniprot.org/uniprot/96RI8 ),  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_172  (Trace amine receptor 5, GPR102:  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:14964 ,  http://www.uniprot.org/uniprot/Q969N4 ) and  http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_173 \n http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115#show_object_173  (trace amine associated receptor 9:  https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:20977 ,  http://www.uniprot.org/uniprot/96RI9 ) are lacking. The thyronamines, endogenous derivatives of thyroid hormone, have affinity for rodent cloned trace amine receptors, including TA 1  [ http://www.ncbi.nlm.nih.gov/pubmed/15146179?dopt=AbstractPlus ]. An antagonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5457  has recently been described with a  p Ki of 9.1 at the mouse TA 1  but >5.3 for human TA 1  [ http://www.ncbi.nlm.nih.gov/pubmed/21237643?dopt=AbstractPlus ].\nMaguire JJ  et al . (2009) International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature.  Pharmacol. Rev. \n 61 : 1‐8 [ https://www.ncbi.nlm.nih.gov/pubmed/19325074?dopt=AbstractPlus ]\nPei Y  et al . (2016) Trace Amines and the Trace Amine‐Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications.  Front Neurosci \n 10 : 148 [ https://www.ncbi.nlm.nih.gov/pubmed/27092049?dopt=AbstractPlus ]\n\nThe urotensin‐II (U‐II) receptor (UT,  nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on the Urotensin receptor  [ 516 ,  http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/25535277?dopt=AbstractPlus ]) is activated by the endogenous dodecapeptide  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2153  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12636 ,  http://www.uniprot.org/uniprot/O95399 ), originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [ http://www.ncbi.nlm.nih.gov/pubmed/2864726?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/20633133?dopt=AbstractPlus ]. Several structural forms of U‐II exist in fish and amphibians. The goby orthologue was used to identify U‐II as the cognate ligand for the predicted receptor encoded by the rat gene  gpr14  [ http://www.ncbi.nlm.nih.gov/pubmed/9861051?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10581185?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10548501?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10559967?dopt=AbstractPlus ]. Human  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2153 ), an 11‐amino‐acid peptide [ http://www.ncbi.nlm.nih.gov/pubmed/9861051?dopt=AbstractPlus ], retains the cyclohexapeptide sequence of goby U‐II that is thought to beimportant in ligand binding [ http://www.ncbi.nlm.nih.gov/pubmed/12807997?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12203418?dopt=AbstractPlus ]. This sequence is also conserved in the deduced amino‐acid sequence of rat  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2155  {Rat} (14 amino‐acids) and mouse  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2154  {Mouse} (14 amino‐acids), although the N‐terminal is more divergent from the human sequence [ http://www.ncbi.nlm.nih.gov/pubmed/10486557?dopt=AbstractPlus ]. A second endogenous ligand for the UT has been discovered in rat [ http://www.ncbi.nlm.nih.gov/pubmed/17628210?dopt=AbstractPlus ]. This is the  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2156  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30894 ,  http://www.uniprot.org/uniprot/Q765I0 ), an octapeptide that is derived from a different gene, but shares the C‐terminal sequence (CFWKYCV) common to U‐II from other species. Identical sequences to rat  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2156 ) are predicted for the mature mouse and human peptides [ http://www.ncbi.nlm.nih.gov/pubmed/18710417?dopt=AbstractPlus ]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [ http://www.ncbi.nlm.nih.gov/pubmed/25535277?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=365 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4468 ,  http://www.uniprot.org/uniprot/Q9UKP6 \n Endogenous agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2156  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:30894 ,  http://www.uniprot.org/uniprot/Q765I0 ) [ http://www.ncbi.nlm.nih.gov/pubmed/18710417?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11015293?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2153  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12636 ,  http://www.uniprot.org/uniprot/O95399 ) [ http://www.ncbi.nlm.nih.gov/pubmed/15852036?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11976263?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12238917?dopt=AbstractPlus ] Selective agonists [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2160 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12238917?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2152 ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9436 ) [ http://www.ncbi.nlm.nih.gov/pubmed/12943190?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9441  [ http://www.ncbi.nlm.nih.gov/pubmed/27791374?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3501  [ http://www.ncbi.nlm.nih.gov/pubmed/19481466?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17112638?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2151  [ http://www.ncbi.nlm.nih.gov/pubmed/12408704?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15781415?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2167  (p K \n i  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/14645137?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9438  (p K \n i  7.2) [ http://www.ncbi.nlm.nih.gov/pubmed/18082287?dopt=AbstractPlus ] – Rat,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3516  (pIC 50  7.1) [ http://www.ncbi.nlm.nih.gov/pubmed/15146030?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3531  (p K \n i  6.6) [ http://www.ncbi.nlm.nih.gov/pubmed/16171813?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9439 ) (p K \n i  6.4) [ http://www.ncbi.nlm.nih.gov/pubmed/17125276?dopt=AbstractPlus ] – Rat Labelled ligands [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2158 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10499587?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/1546952?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17125276?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11015293?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9440 ) [ http://www.ncbi.nlm.nih.gov/pubmed/22044114?dopt=AbstractPlus ]\nIn the human vasculature, human  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2153  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12636 ,  http://www.uniprot.org/uniprot/O95399 ) elicits both vasoconstrictor (p D \n 2  9.3‐10.1, [ http://www.ncbi.nlm.nih.gov/pubmed/11015293?dopt=AbstractPlus ]) and vasodilator (pIC 50  10.3‐10.4, [ http://www.ncbi.nlm.nih.gov/pubmed/11158995?dopt=AbstractPlus ]) responses.\nFoord SM  et al.  (2005) International Union of Pharmacology. XLVI. G protein‐coupled receptor list.  Pharmacol Rev \n 57:  279‐288[ https://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]\nHunt BD  et al.  (2010) A rat brain atlas of urotensin‐II receptor expression and a review of central urotensin‐II effects.  Naunyn Schmiedebergs Arch. Pharmacol. \n 382 :1‐31[ https://www.ncbi.nlm.nih.gov/pubmed/20422157?dopt=AbstractPlus ]\nMaryanoff BE  et al.  (2010) Urotensin‐II receptor modulators as potential drugs.  J. Med. Chem. \n 53:  2695‐708[ https://www.ncbi.nlm.nih.gov/pubmed/20043680?dopt=AbstractPlus ]\nRoss B  et al.  (2010) Role of urotensin II in health and disease.  Am.J.Physiol.Regul.Integr.Comp. Physiol. \n 298:  R1156‐72[ https://www.ncbi.nlm.nih.gov/pubmed/20421634?dopt=AbstractPlus ]\nVaudry H  et al.  (2015) International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II‐related peptide, and their receptor: from structure to function.  Pharmacol. Rev. \n 67:  214‐58[ https://www.ncbi.nlm.nih.gov/pubmed/25535277?dopt=AbstractPlus ]\n\nVasopressin (AVP) and oxytocin (OT) receptors ( nomenclature as recommended by  NC‐IUPHAR  [ http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus ]) are activated by the endogenous cyclic nonapeptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2168  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:894 ,  http://www.uniprot.org/uniprot/P01185 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2174  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8528 ,  http://www.uniprot.org/uniprot/P01178 ). These peptides are derived from precursors which also produce neurophysins (neurophysin I for oxytocin; neurophysin II for vasopressin). Vasopressin and oxytocin differ at only 2 amino acids (positions 3 and 8). There are metabolites of these neuropeptides that may be biologically active [ http://www.ncbi.nlm.nih.gov/pubmed/8258377?dopt=AbstractPlus ].\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=366 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=367 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:895 ,  http://www.uniprot.org/uniprot/P37288 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:896 ,  http://www.uniprot.org/uniprot/P47901 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2168  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:894 ,  http://www.uniprot.org/uniprot/P01185 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2174  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8528 ,  http://www.uniprot.org/uniprot/P01178 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15084136?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10866830?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10780976?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9264324?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8106369?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2168  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:894 ,  http://www.uniprot.org/uniprot/P01185 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2174  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8528 ,  http://www.uniprot.org/uniprot/P01178 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15084136?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12446593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10780976?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9264324?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9322919?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2171  [ http://www.ncbi.nlm.nih.gov/pubmed/11934825?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10866830?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2191  [ http://www.ncbi.nlm.nih.gov/pubmed/17300166?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2187  [ http://www.ncbi.nlm.nih.gov/pubmed/12446593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ] Antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2203  (p K \n i  8.2–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459574?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2202  (p K \n i  8.4–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11861823?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2200  (p K \n i  8.1–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10866830?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8106369?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3867  (p K \n i  9) – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2207  (Antagonist) (p K \n d  10.3–10.4) [ http://www.ncbi.nlm.nih.gov/pubmed/7774575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10866830?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2175 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11337500?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7774575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8106369?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3813  (Antagonist) (p K \n d  9) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2175 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/12446593?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9264324?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9322919?dopt=AbstractPlus ] \n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=368 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=369 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:897 ,  http://www.uniprot.org/uniprot/P30518 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8529 ,  http://www.uniprot.org/uniprot/P30559 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2168  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:894 ,  http://www.uniprot.org/uniprot/P01185 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2174  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8528 ,  http://www.uniprot.org/uniprot/P01178 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/15084136?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7774575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/17300166?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11012895?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9864265?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2174  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:8528 ,  http://www.uniprot.org/uniprot/P01178 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2168  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:894 ,  http://www.uniprot.org/uniprot/P01185 ) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7774575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8955347?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/12660315?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7475979?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7921228?dopt=AbstractPlus ] Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3537  [ http://www.ncbi.nlm.nih.gov/pubmed/16297621?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2173  [ http://www.ncbi.nlm.nih.gov/pubmed/10780976?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3869 \n [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2179  [ http://www.ncbi.nlm.nih.gov/pubmed/8955347?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/2827511?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7475979?dopt=AbstractPlus ] Antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2252  (p K \n i  8.8) [ http://www.ncbi.nlm.nih.gov/pubmed/16158071?dopt=AbstractPlus ] Selective antagonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2203  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/20471258?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2226  (p K \n i  9.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9864265?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2199  (p K \n i  8.4–9.3) [ http://www.ncbi.nlm.nih.gov/pubmed/10519430?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9792651?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/8981918?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11012895?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2238  (Inverse agonist) (p K \n i  8.9–9.2) [ http://www.ncbi.nlm.nih.gov/pubmed/9651149?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2236  (p K \n i  6.9–8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9792651?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2197  (Inverse agonist) (p K \n i  7.4–8.1) [ http://www.ncbi.nlm.nih.gov/pubmed/9792651?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9322919?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2201  (p K \n i  8.8–9.1) [ http://www.ncbi.nlm.nih.gov/pubmed/14722330?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3870  (p K \n i  8.5),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2253  (p K \n i  8.4) [ http://www.ncbi.nlm.nih.gov/pubmed/9622556?dopt=AbstractPlus ] Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2175 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/9792651?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10780976?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9884074?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9459574?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/9864265?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2228  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/2964362?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3817  (p K \n d  8.6) [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3778  (Antagonist) (p K \n d  10),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2176 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/7774575?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/6278592?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7475979?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/7921228?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3756  (p K \n d  8.3) [ http://www.ncbi.nlm.nih.gov/pubmed/12942128?dopt=AbstractPlus ]\nVasopressin and oxytocin receptors have a characteristic and sometimes overlapping distribution in a number of tissues including brain. There are phylogenetic, ontogenetic and sex‐specific differences in the levels and distribution of these receptors, particularly in the brain. The V 2  receptor exhibits marked species differences, such that many ligands ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2236  and [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3817 ) exhibit low affinity at human V 2  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/9773787?dopt=AbstractPlus ]. Similarly,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2170  is more V 2  selective in the rat than in the human [ http://www.ncbi.nlm.nih.gov/pubmed/9264324?dopt=AbstractPlus ]. The gene encoding the V 2  receptor is polymorphic in man, underlying nephrogenic diabetes insipidus [ http://www.ncbi.nlm.nih.gov/pubmed/9756088?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2187  is selective only for the human and bovine V 1 B receptors [ http://www.ncbi.nlm.nih.gov/pubmed/12446593?dopt=AbstractPlus ], while  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2191  has high affinity for the rat V 1 B receptor [ http://www.ncbi.nlm.nih.gov/pubmed/17300166?dopt=AbstractPlus ]. Knockouts of vasopressin and oxytocin receptors have systemspecific defects (e.g., impaired ability toconcentrate urine in V 2  receptor knockouts) which include behavioural deficits (principally in V 1 A , V \n 1 B and OT receptor knockouts).\nKnepper MA. (2012) Systems biology in physiology: the vasopressin signaling network in kidney.  Am. J. Physiol., Cell Physiol. \n 303:  C1115‐24[ https://www.ncbi.nlm.nih.gov/pubmed/22932685?dopt=AbstractPlus ]\nKoshimizu TA  et al.  (2012) Vasopressin V1a and V1b receptors: from molecules to physiological systems.  Physiol. Rev. \n 92:  1813‐64[ https://www.ncbi.nlm.nih.gov/pubmed/23073632?dopt=AbstractPlus ]\nManning M  et al.  (2012) Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics.  J. Neuroendocrinol. \n 24:  609‐28[ https://www.ncbi.nlm.nih.gov/pubmed/22375852?dopt=AbstractPlus ]\nMeyer‐Lindenberg A  et al.  (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine.  Nat. Rev. Neurosci. \n 12:  524‐38[ https://www.ncbi.nlm.nih.gov/pubmed/21852800?dopt=AbstractPlus ]\nNeumann ID  et al.  (2012) Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors.  Trends Neurosci. \n 35:  649‐59[ https://www.ncbi.nlm.nih.gov/pubmed/22974560?dopt=AbstractPlus ]\n\nVasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating peptide (PACAP) receptors ( nomenclature as agreed by the  NC‐IUPHAR  Subcommittee on Vasoactive Intestinal Peptide Receptors  [ http://www.ncbi.nlm.nih.gov/pubmed/9647867?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/22289055?dopt=AbstractPlus ]) are activated by the endogenous peptides  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12693 ,  http://www.uniprot.org/uniprot/P01282 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257 ), peptide histidine isoleucineamide ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4397  {Mouse, Rat}), peptide histidine methionineamide ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2274 )) and peptide histidine valine ( http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3706 )). VPAC 1  and VPAC 2  receptors display comparable affinity for the PACAP peptides,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 ), and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12693 ,  http://www.uniprot.org/uniprot/P01282 ), whereas  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 ) are >100 fold more potent than  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152 ) as agonists of most isoforms of the PAC 1  receptor. However, one splice variant of the human PAC 1  receptor has been reported to respond to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152 ) with comparable affinity [ http://www.ncbi.nlm.nih.gov/pubmed/10583729?dopt=AbstractPlus ].  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2272  [ http://www.ncbi.nlm.nih.gov/pubmed/11068102?dopt=AbstractPlus ] has been used as a selective VPAC 2  receptor antagonist in a number of physiological studies, but has been reported to have significant activity at VPAC 1  and PAC 1  receptors [ http://www.ncbi.nlm.nih.gov/pubmed/16930633?dopt=AbstractPlus ]. The selective PAC 1  receptor agonist  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2264 , was extracted from the salivary glands of sand flies ( Lutzomyia longipalpis ) and has no sequence homology to  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152 ) or the PACAP peptides [ http://www.ncbi.nlm.nih.gov/pubmed/8995389?dopt=AbstractPlus ]. Two deletion variants of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2264 ,  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3305  [ http://www.ncbi.nlm.nih.gov/pubmed/9928019?dopt=AbstractPlus ] and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2265  [ http://www.ncbi.nlm.nih.gov/pubmed/10438479?dopt=AbstractPlus ] have been reported to be PAC 1  receptor antagonists, but these peptides have not been extensively characterised.\n Nomenclature \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=370 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=371 \n \n http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=372 \n HGNC, UniProt \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:242 ,  http://www.uniprot.org/uniprot/P41586 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12694 ,  http://www.uniprot.org/uniprot/P32241 \n \n https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12695 ,  http://www.uniprot.org/uniprot/P41587 \n Potency order of endogenous ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 )  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12693 ,  http://www.uniprot.org/uniprot/P01282 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12693 ,  http://www.uniprot.org/uniprot/P01282 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 )  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2270  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4265 ,  http://www.uniprot.org/uniprot/P01286 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2273  {Pig},  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10607 ,  http://www.uniprot.org/uniprot/P09683 ) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1152  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:12693 ,  http://www.uniprot.org/uniprot/P01282 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ) >  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2273  {Pig} ≫  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2270  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:4265 ,  http://www.uniprot.org/uniprot/P01286 ),  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3643  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:10607 ,  http://www.uniprot.org/uniprot/P09683 ) Selective agonists \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2264  [ http://www.ncbi.nlm.nih.gov/pubmed/16930633?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2264 ] [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3842  [ http://www.ncbi.nlm.nih.gov/pubmed/11931347?dopt=AbstractPlus ], [ http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2278  [ http://www.ncbi.nlm.nih.gov/pubmed/10801840?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2259  [ http://www.ncbi.nlm.nih.gov/pubmed/9145428?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10570056?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/11931347?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2276  [ http://www.ncbi.nlm.nih.gov/pubmed/9152366?dopt=AbstractPlus ] Selective antagonists – \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2268  (pIC 50  8.7) [ http://www.ncbi.nlm.nih.gov/pubmed/9437716?dopt=AbstractPlus ,  http://www.ncbi.nlm.nih.gov/pubmed/10570056?dopt=AbstractPlus ] – Labelled ligands \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2261  (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/11193823?dopt=AbstractPlus ] \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2277 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10801840?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2261  (Agonist) \n http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2277 ) (Agonist) [ http://www.ncbi.nlm.nih.gov/pubmed/10801840?dopt=AbstractPlus ],  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2261  (Agonist)\nSubtypes of PAC 1  receptors have been proposed based on tissue differences in the potencies of  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2257  ( https://www.genenames.org/data/gene‐symbol‐report/#!/hgnc_id/HGNC:241 ,  http://www.uniprot.org/uniprot/P18509 ) and  http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2258 ); these might result from differences in G protein coupling and second messenger mechanisms [ http://www.ncbi.nlm.nih.gov/pubmed/8967982?dopt=AbstractPlus ], or from alternative splicing of PAC 1  receptor mRNA [ http://www.ncbi.nlm.nih.gov/pubmed/8396727?dopt=AbstractPlus ].\nHarmar AJ  et al.  (1998) International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide.  Pharmacol Rev \n 50:  265‐270[ https://www.ncbi.nlm.nih.gov/pubmed/9647867?dopt=AbstractPlus ]\nHarmar AJ  et al.  (2012) Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide: IUPHAR review 1.  Br. J. Pharmacol. \n 166:  4‐17[ https://www.ncbi.nlm.nih.gov/pubmed/22289055?dopt=AbstractPlus ]\nReglodi D  et al.  (2012) Effects of pituitary adenylate cyclase activating polypeptide in the urinary system, with special emphasis on its protective effects in the kidney.  Neuropeptides \n 46:  61‐70[ https://www.ncbi.nlm.nih.gov/pubmed/21621841?dopt=AbstractPlus ]\nSmith CB  et al.  (2012) Is PACAP the major neurotransmitter for stress transduction at the adrenomedullary synapse?  J. Mol. Neurosci. \n 48:  403‐12[ https://www.ncbi.nlm.nih.gov/pubmed/22610912?dopt=AbstractPlus ]","source_license":"CC-BY-4.0","license_restricted":false}