Effect of GABA, GABA agonists and antagonists on gastric ulcer in rats

ABSTRACT

In the present investigation the effect of gamma-aminobutyric acid [GABA] on indomethacin [IM] [25 mg/kg orally] induced gastric ulcer in rats was studied. Results revealed that GABA at doses of 75 mg/kg [I.P.] and 150 mg/kg [I.P.] were devoid of significant effect on IM-induced ulceration, mean while higher doses of GABA 300 mg/kg [I.P.] and [450 mg/kg [I.P.] potentiated IM-ulceration. Regarding the effect of GABA antagonists, data proved that picrotoxin [2.5 mg/kg I.P] bicuculline [2.5 mg/kg I.P.] and pentylenetetrazole [PTZ] [25 mg/kg I.P.] blocked the aggravating effect of GABA on IM-induced gastric ulceration. It was noticed that GABA antagonists produced no significant changes on IM-ulceration. Also diazepam [0.5 mg/kg I.P.] and pentobarbital [5 mg/kg I.P.] potentiated the exacerbating effect of GABA on IM-induced gastric ulceration. At the same time both diazepam and pentobarbital were devoid of significant effect on IM-ulceration. In contrast GABA agonist muscimol [6 mg/kg orally] had cytoprotective effect against IM-induced gastric ulceration, while GABA agonist baclofen [6 mg/kg orally] showed no significant effect on IM- ulceration However, atropine [1 mg/kg I.P.] was protective against both IM-induced gastric ulceration and the GABA potentiating effect of IM -ulceration. The results suggested that GABA induced exacerbation of IM -ulceration might be due to the activation of peripheral muscarinic receptors in the stomach. This effect was mediated by stimulation of GABA[A] .-receptors and not GABA receptors in the stomach