Effects of hydralazine and verapamil on phosphorylase activity and guanosine cyclic 3',5'-monophosphate levels in guinea-pig taenia coli.

1 The roles of guanosine cyclic 3',5'-monophosphate (cyclic GMP) and calcium in the relaxation produced by hydralazine and verapamil in potassium-depolarized guinea-pig taenia coli have been investigated.2 Depolarization of isolated strips of guinea-pig taenia coli by 124 mM KCl caused sustained contractures and increases in tissue levels of cyclic GMP.3 The KCl-induced increases in cyclic GMP levels appeared to be calcium dependent. No increases in cyclic GMP levels were seen in strips of taenia coli depolarized in the absence of calcium. Readdition of calcium to the depolarizing solution contracted the muscles and increased cyclic GMP levels. When calcium was removed from the depolarizing solution during the sustained, tonic phase of a KCl-induced contracture, both tension and cyclic GMP levels returned to control values.4 Administration of 50 muM verapamil to KCl-contracted muscles completely relaxed the muscles and caused cyclic GMP levels to return to control values within 14 min. Hydralazine, 2 mM, on the other hand, relaxed the depolarized muscles without lowering cyclic GMP levels. No significant changes in cyclic AMP levels were seen in any of these experiments.5 Similar results were obtained in an analogous series of experiments in which glycogen phosphorylase activity was measured instead of cyclic GMP levels. Activation of phosphorylase during contractions of guinea-pig taenia coli had previously been reported to be a calcium-dependent phenomenon.6 It was concluded that increases in tissue levels of cyclic GMP (or of cyclic AMP) were not responsible for the relaxant effects of hydralazine or verapamil in these experiments. It was also suggested, based on our results, that verapamil exerted its relaxant effects in the depolarized taenia coli by lowering cytoplasmic calcium levels, whereas hydralazine relaxed the depolarized muscles without lowering intracellular calcium activity.