Specific H+/K(+)-ATPase inhibitors decreased contractile responses of isolated rat vas deferens.
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 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+).
Yenişehirli
Aydan
A
Department of Pharmacology, Faculty of Medicine, Gaziosmanpaşa University, Kişla yolu 60100, Tokat, Turkey. aydany@hacettepe.edu.tr
Onur
Rüştü
R
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009853:Omeprazole / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D054328:Proton Pump Inhibitors; C035235:Sch 28080; D064747:Lansoprazole; D010656:Phenylephrine; D010042:Ouabain; D009853:Omeprazole; D011188:Potassium; D002118:Calcium