Effect of cyclic nucleotide phosphodiesterase regulators on isolated rat uterus: with observations on their mechanism of action.

The effect of PDE regulators on isolated rat uterus and their probable mechanism of action was investigated. The potassium chloride-induced contracture was enhanced by imidazole (3.67 X 10(-3)M) and potassium bicarbonate (1.5 X 10(-2)M). In contrast, imidazole (pH adjusted with potassium dihydrogen orthophosphate or HCl) produced a biphasic effect, i.e. initial transient relaxation followed by a sustained contracture. A similar biphasic effect of imidazole was observed in uterine preparations suspended in calcium free K2SO4-Ringer, but in preparations which were allowed to equilibrate to a new base line, it produced sustained contracture. The imidazole-induced increase in contracture appears to be mediated through increased influx of calcium. Phosphodiesterase (PDE) stimulation plays only a minor role, if any. The transient relaxant effect of imidazole may be due to inhibition of thromboxane synthetase and the resultant decrease of intracellular calcium release. The relaxant effect of PDE inhibitors (aminophylline, papaverine, diazoxide), catecholamines and db-cyclic AMP on the K2SO4-Ringer and calcium chloride induced contracture was antagonized by imidazole (pH adjusted with HCl). This inhibitory effect of PDE inhibitors may be mediated through the altered membrane permeability to calcium.