GABA-mimetic effect on gastric acid secretion. Possible significance in central mechanisms.
Parenteral administration of beta-(p-chlorophenyl)-gamma-aminobutyric acid (PCP-GABA), a lipophilic GABA mimetic, has been shown to aggravate stress-induced ulcerations in the rat. Since acid hypersecretion may be a possible mechanism for this, we studied the effect of graded doses of PCP-GABA on rat gastric acid secretion. The stimulatory effect of PCP-GABA was found to be dose-dependent, long-acting, and massive, exceeding the maximal effects of histamine and bethanechol. The acid stimulant effect of PCP-GABA was completely abolished not only by atropine but also by truncal vagotomy. Vagotomized, PCP-GABA-treated animals responded to bethanechol, suggesting that a peripheral (cellular) mechanism is not involved. We conclude that PCP-GABA acts centrally to activate vagal centers and to cause acid hypersecretion. Although hypersecretion of acid caused by PCP-GABA may be involved in the observed aggravation of stress-induced ulceration in the rat stomach, evidence for this has yet to be provided.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D001626:Bethanechol Compounds; D001285:Atropine; D001418:Baclofen