Specific H +/K +-ATPase inhibitors decreased contractile responses of isolated rat vas deferens

Abstract

The effect of H +/K +-ATPase inhibitors on rat vas deferens contractility was investigated in vitro. Omeprazole (100–300 μM), lansoprazole (100–300 μM) and SCH 28080 (10–100 μM) (2-methyl-8-(phenylmethoxy)-imidazo[1,2-a]pyridine-3-acetonitrile) decreased contractile responses of vas deferens to electrical field stimulation, high K + (80 mM) and phenylephrine in a reversible, reproducible and concentration-dependent manner. The inhibitory potency of lansoprazole on vas deferens contractility was increased in relatively acidic solution (pH 6.9), suggesting that the site of action may be related to H +/K +-ATPase. However, lansoprazole-induced inhibition on contractility was unaltered in K + free solution, indicating that the mechanism of action is independent from H +/K +-ATPase. Reversible nature of omeprazole and lansoprazole-induced inhibition on contractility also suggests that the effects are not due to inhibition of H +/K +-ATPase, since both compounds are irreversible inhibitors of the enzyme. Presence of ouabain (5 μM) did not decrease lansoprazole-induced inhibition on contractility but potentiated the inhibitory effect of lansoprazole, suggesting that lansoprazole-induced inhibition is not mediated by the inhibition of Na +/K +-ATPase. Calcium-induced contractions in high K +–Ca 2+ free medium were completely antagonized by lansoprazole, implying that lansoprazole inhibits Ca 2+ entry through voltage-gated channels. In conclusion, three H +/K +-ATPase inhibitors decreased contractile responses of rat vas deferens to various stimulants in vitro. They may act on a common mechanism, which plays a crucial role in regulating rat vas deferens contractility and this mechanism is probably involved in the regulation of intracellular Ca 2+.