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 (100-300microM), lansoprazole (100-300microM) and SCH 28080 (10-100microM) (2-methyl-8-(phenylmethoxy)-imidazo[1,2-a]pyridine-3-acetonitrile) decreased contractile responses of vas deferens to electrical field stimulation, high K(+) (80mM) 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 (5microM) 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…
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