Stimulatory effect of diazepam on gastric acid secretion in the continuously perfused stomach in rats under urethane anesthesia.

The effects of diazepam, a typical benzodiazepine receptor agonist, on gastric acid secretion were studied in both conscious pylorus-ligated rats and the perfused stomach of rats under urethane anesthesia. Diazepam did not affect acid secretion in conscious pylorus-ligated rats. Under urethane anesthesia, diazepam showed a definite stimulation on gastric acid secretion. However this stimulatory action was caused neither by 4'-chlordiazepam, which is a peripheral benzodiazepine receptor agonist, nor beta-carbline-3-carboxylic acid methyl ester, which is an inverse benzodiazepine receptor agonist. Pretreatment with atropine, hexamethonium or bilateral truncal vagotomy inhibited the diazepam-induced acid secretion. Pretreatment with flumazenil, which is a benzodiazepine receptor antagonist, reduced the acid secretion induced by diazepam, but pretreatment with 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide, which is a peripheral benzodiazepine receptor antagonist, did not reduce the acid secretion induced by diazepam. 3-Mercaptopropionic acid, which is an inhibitor of GABA biosynthesis, picrotoxin and pentylenetetrazol inhibited diazepam-stimulated acid secretion. Gastric acid secretion stimulated by baclofen was not affected by flumazenil, 3-mercaptopropionic acid or picrotoxin. These results suggest that acid secretion is centrally stimulated by diazepam in rats under anesthesia, and the stimulatory action is closely associated with benzodiazepine-GABA complex receptors.