Cholecystokinin antagonism by benzodiazepines in the contractile response of the isolated guinea-pig gallbladder.

Three benzodiazepines, chlordiazepoxide (CDP), diazepam (DZP) and medazepam (MZP), inhibited the contractile response of circular muscle strips from the isolated guinea-pig gallbladder to sulfated cholecystokinin octapeptide (CCK8) in the presence of atropine. The dose-response curves for CCK8 were shifted in parallel to the right by 10(-6) to 10(-5) M of the three benzodiazepines, although the maximum response to CCK8 was depressed by higher concentrations. Schild plot analysis of the antagonism gave pA2 values of 6.70 for CDP and 7.33 for DZP and slopes of the regression lines close to 1.0, suggesting that the antagonism was competitive in nature. The responses to acetylcholine, histamine and bradykinin were also depressed by 10(-5) M of DZP, but no parallel shift of their dose-response curves was observed. The non-specific inhibitory action of the benzodiazepines on these agonists was presumed to be due to the calcium antagonist-like action of the benzodiazepines. The antagonism between CCK8 and the benzodiazepines in the gallbladder was unaffected by GABA.