gamma-Aminobutyric acid stimulates acid secretion from the isolated guinea pig stomach.

gamma-Aminobutyric acid (GABA) content was measured, and the effect of GABA on acid secretion was studied using the everted preparation of isolated guinea pig stomachs. GABA contents in the mucosa layer and the remaining layer were 20-24 nmol/g tissue and 34-42 nmol/g tissue, respectively. GABA at 10(-6) to 3 X 10(-5) M induced acid secretion, and the maximum secretion was obtained at 3 X 10(-5) M, that is approximately 1.6-fold of the spontaneous secretion and approximately half of the amount secreted by histamine at 3 X 10(-4) M. The GABA-induced acid secretion was inhibited by bicuculline, scopolamine, pirenzepine, proglumide, and tetrodotoxin, but not by cimetidine. Muscimol (3 X 10 to 10(-5) M), but not baclofen, induced acid secretion in a concentration-dependent manner. The responses to GABA and muscimol were antagonized by bicuculline. Scopolamine and tetrodotoxin completely inhibited the acid secretion induced by low concentrations of GABA and muscimol and to some extent the response induced by high concentrations of muscimol. All these results indicate that GABA induces acid secretion via the A type of GABA receptor, probably located mainly on the cholinergic neurons and partially on the nonneuronal cells in the guinea pig stomach.