Investigation of the relaxant effects of pinacidil and Cromakalim on the sheep sphincter of Oddi

Abstract

Background/Aims: ATP-sensitive K+ (KATP) channels play an important role in the regulation of smooth muscle membrane potential. This study was designed to investigate the effects of pinacidil and cromakalim, KATP-sensitive channel activators, on sheep sphincters of Oddi ( SO). Methods: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to pinacidil (10(-9) - 10(-4) M) and cromakalim (10(-9) - 10(-4) M) in the presence or absence of glibenclamide (10(-6) M), a blocker of KATP channels. Furthermore, concentration-dependent contraction responses of carbachol were obtained. Results: Carbachol (10(-9) - 10(-5) M) induced concentration-dependent contraction responses in the SO rings. Pinacidil (10(-9) - 10(-4) M) and cromakalim (10(-9) - 10(-4) M) induced concentration-dependent relaxation in isolated SO rings precontracted with carbachol (10(-6) M). At their maximum effects, both pinacidil and cromakalim produced nearly full relaxation. In the presence of glibenclamide, concentration-relaxation curves for pinacidil and cromakalim underwent rightward parallel shifts. There were no significant differences between pEC(50) and E-max values of pinacidil and cromakalim in the absence of glibenclamide (10(-6) M) ( p > 0.05), but pEC(50) values of pinacidil and cromakalim in the presence of glibenclamide (10(-6) M) were signifi cantly reduced ( p < 0.05). Conclusion: These results suggest that the relaxation caused in sheep SO by pinacidil and cromakalim is mediated through the same glibenclamide-sensitive KATP channel. Pinacidil and cromakalim have an equipotent relaxing effect in isolated sheep SO and they can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies. Copyright (C) 2006 S. Karger AG, Basel and IAP.