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);a selective CCK-A receptor antago-nist, devazepide(L-364,781);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 pylorous-ligated rats. Intravenous administration of L-365, 260, L-364, 781 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(5µmol/kg/hr) with ED50 values of 5.9 and 4.3 µmol/kg, respectively.L-364,781 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 tretment with L-365,260(3-100 µmol/kg, i.v) and cimetidine(11.9396.4 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.
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