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.
Lin
W C
WC
Department of Pharmacology, China Medical College, Taichung, Taiwan, R.O.C.
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011708:Pylorus / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D014520:Urethane; D014628:Vagotomy
D015097:3-Mercaptopropionic Acid; D018686:Anesthetics, Intravenous; D001285:Atropine; D003975:Diazepam; D005442:Flumazenil; D018682:GABA Agents; D018756:GABA Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D018738:Hexamethonium; D007546:Isoquinolines; D010276:Parasympatholytics; D010433:Pentylenetetrazole; D010852:Picrotoxin; D018079:Receptors, GABA; D014520:Urethane; C037850:PK 11195