Involvement of central type benzodiazepine and GABAA receptor in the protective effect of benzodiazepines in stress-induced gastric ulcers in rats.
Various benzodiazepines (BZs) were studied for ulcer protective effect in immobilization stress-induced gastric ulcers in rats. Central type BZ receptor agonists such as clonazepam, chlorodiazepoxide and diazepam shared marked antiulcer effect. The ulcer protective action of these agents was reversed by pretreatment with Ro 15-1788, a central BZ receptor antagonist. However, peripheral BZ receptor binding agent Ro 5-4864 and BZ-micromolar binding agent phenytoin, failed to show any antiulcer effect. Pretreatment with bicuculline also reversed the ulcer protective action of central type BZ receptor agonists. A bicuculline sensitive potentiation was observed in the ulcer protective effect of central BZ receptor agonist, when a subeffective dose was combined with muscimol, a specific GABAA agonist. But no such potentiation was seen with baclofen, a GABAB agonist. These data imply an interaction of central type BZ receptor with GABAA subtype receptor in the ulcer protective effect of benzodiazepines in rats.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005753:Gastric Mucosa / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000503:physiopathology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications*
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D005442:Flumazenil