Effects of the pannexin-1 hemichannel inhibitor probenecid on rat enteric glial cells following intestinal ischemia and reperfusion

Abstract Background : This study examined the effects of probenecid (PB), a pannexin-1 channel antagonist, on the enteric glial cells of the rat ileum after ischemia and reperfusion. Methods: The ileal vessels were occluded for 45 min with atraumatic vascular clamps, and the tissue was then reperfused for periods of 24 h and 14 and 28 days. After ischemia, the animals were either left without further treatment (IR groups) or treated with PB (PB groups). Results: The results demonstrated that glial cells were immunoreactive for S100β and/or GFAP and that the pannexin-1 channel was present in glial cells. Density analyses (in cells/cm2) showed that the IR groups exhibited a decrease in the numbers of cells immunoreactive for pannexin-1 and HuC/D and that treatment with PB caused their numbers to recover. The number of glial cells (S100β and GFAP) was elevated in the IR group, and PB treatment decreased the total number of glia, but the number of S100β-positive glia did not recover. Additionally, the cell profile area (μm2) of S100β-positive glial cells showed no recovery in the PB groups. The contractile activity of the ileum was decreased in the IR groups and restored in the PB groups. Conclusions: PB can effectively induce the recovery of neurons and glial cells and is thus a potential therapeutic agent for diseases of the gastrointestinal tract.