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


Yenisehirli A., Onur R.

PHARMACOLOGICAL RESEARCH, vol.54, no.6, pp.397-405, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 54 Issue: 6
  • Publication Date: 2006
  • Doi Number: 10.1016/j.phrs.2006.07.005
  • Title of Journal : PHARMACOLOGICAL RESEARCH
  • Page Numbers: pp.397-405

Abstract

The effect of H+/K+-ATPase inhibitors on rat vas deferens contractility was investigated in vitro. Omeprazole (100-300 mu M), lansoprazole (100-300 mu M) and SCH 28080 (10-100 mu M) (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 ouabam (5 mu M) 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+-Ca2+ free medium were completely antagonized by lansoprazole, implying that lansoprazole inhibits Ca2+ 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 Ca2+. (c) 2006 Elsevier Ltd. All rights reserved.