Abstract
We evaluated the effects of a potent cholecystokinin (CCK)-B/gastrin receptor antagonist, L-365, 260 (3R(+)-N-(2, 3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl)-N''-(3-methylphenyl)urea); a selective CCK-A receptor antagonist, devazepide (L-364, 718); and cimetidine on gastric acid secretion induced by pentagastrin, histamine and bethanechol in anesthetized rats. We also evaluated the effects of L-365, 260 and cimetidine on acid secretion in pylorus-ligated rats. Intravenous administration of L-365, 260, L-364, 718 and cimetidine dose-dependently reduced acid secretion induced by pentagastrin (20 nmol/kg/hr), with ED50 values of 0.63, 19.1 and 2.5 μmol/kg, respectively. Of interest was the finding that L-365, 260, like cimetidine, dose-dependently inhibited acid secretion induced by histamine (100 μmol/kg/hr) and bethanechol (5 μmol/kg/hr) with ED50 values of 5.9 and 4.3 μmol/kg, respectively. L-364, 718, even at 30 μmol/kg, i.v., had only a slight effect on histamine or bethanechol-induced acid secretion. Gastric acid secretion was suppressed by treatment with L-365, 260 (3-100 μmol/kg, i.v.) and cimetidine (11.9-396.4 μmol/kg, i.v.) in pylorus-ligated rats, with ED50 values of 13.3 and 96.9 μmol/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.
