ABSTRACT-We evaluated the effects of a potent cholecystokinin (CCK)-B/gastrin receptor antagonist, L-365,260 (3R(+)-N-(2,3-dihydro-l-methyl-2-oxo-5-phenyl-lH 1,4-benzodiazepin-3-yl)-N'-(3-methylphenyl)urea); a selective CCK-A receptor antago nist, devazepide (L-364,718); and cimetidine on gastric acid secretion induced by pen tagastrin, histamine and bethanechol in anesthetized rats. We also evaluated the effects of L-365,260 and cimetidine on acid secretion in pylorus-ligated rats. In travenous administration of L-365,260, L-364,718 and cimetidine dose-dependently re duced acid secretion induced by pentagastrin (20 nmol/kg/hr), with ED50 values of 0.63, 19.1 and 2.5 pmol/kg, respectively. Of interest was the finding that L-365,260, like cimetidine, dose-dependently inhibited acid secretion induced by histamine (100 umol/kg/hr) and bethanechol (5 ,umol/kg/hr) with ED50 values of 5.9 and 4.3 ,umol/kg, respectively. L-364,718, even at 30,umol/kg, i.v., had only a slight effect on histamine or bethanechol-induced acid secretion. Gastric acid secretion was sup pressed by treatment with L-365,260 (3-100 pmol/kg, i.v.) and cimetidine (11.9 396.4 ,u mol/kg, i.v.) in pylorus-ligated rats, with ED50 values of 13.3 and 96.9 ,umol/kg, respectively. These results indicate that L-365,260 suppresses acid secretion induced by histamine and bethanechol in rats and that the gastrin receptor plays an important role in acid secretion in pylorus-ligated rats.Gastrin plays an important role in the gas tric phase of acid secretion in animals (1) and humans (2). There is a good correlation be tween the serum gastrin concentration and the amount of gastric acid secretion during feeding (2, 3). However, few studies have examined the role of gastrin in basal and histamine or cholinomimetic-induced gastric acid secretion, as no potent and selective gastrin receptor antagonists have been developed. Proglumide, which has been reported to be a gastrin recep tor antagonist, inhibits basal (4) and acetyl choline-induced gastric acid secretion (5). However, it is unclear whether endogenous gastrin participates in gastric acid secretion in duced by histamine or cholinomimetics or whether it plays an important role in basal acid secretion, since the gastrin receptor an tagonistic activity of proglumide is very weak and shows low selectivity.