Mechanism of inhibitory effects of ethanol on gallbladder contraction: differences in cases of histamine- and acetylcholine-induced contraction]

We investigated the effects of different concentrations of ethanol on contraction of gallbladder isolated from guinea pig. Ethanol at 25 mM significantly inhibited the contraction induced by histamine, but not those by KCl and acetylcholine. A higher concentration (100 mM) of ethanol inhibited both histamine-, acetylcholine- and KCl- induced contractions. The inhibitory effect of the lower concentration (25 mM) of ethanol was not observed in the presence of verapamil, an antagonist of L-type Ca2+ channel or staurosporine, a selective inhibitor of protein kinase C. Verapamil and staurosporine significantly inhibited both histamine- and acetylcholine-induced contractile responses: the inhibitory effect was more potent for the histamine contraction. Our recent study has demonstrated that contraction caused by protein kinase C activation is completely dependent on Ca2+ influx through the L-type Ca2+ channel in gallbladder smooth muscle of guinea pig. Therefore, the difference in 25 mM ethanol effect on histamine- and acetylcholine-induced contractions may be due to different degree of involvement of protein kinase C activation in the agonist-induced contraction. On the other hands, the higher concentration (100 mM) of ethanol inhibits the common pathway of contraction in gallbladder smooth muscle cells.