γ-Aminobutyric acid localization and function as modulator of cholinergic neurotransmission in rat antral mucosal/submucosal fragments

Abstract

γ-Aminobutyric acid, a neurotransmitter in the central nervous system, has been shown to be present in and synthesized and secreted by rodent and feline myenteric plexus neurons. The aims of the present studies were to measure γ-aminobutyric acid concentrations and synthesis and to establish cellular localization and uptake of γ-aminobutyric acid by immunocytochemistry and autoradiography, respectively, within mucosal and submucosal tissues of the rat antrum. Direct demonstration of [3H]γ-aminobutyric acid release and the effects of exogenous γ-aminobutyric acid and muscimol, a GABAα agonist, on [3H]acetylcholine release from antral mucosal/ submucosal fragments were examined in perifusion experiments. γ-Aminobutyric acid content and synthesis, as reflected by glutamic acid decarboxylase activity, were present within antral mucosa at levels two to three times that of the body and muscular layers of both the gastric body and antrum. γ-Aminobutyric acid was identified immunocytochemically, principally in mucosal epithelial cells of the antrum. Exogenous γ-aminobutyric acid and muscimol were capable of stimulating acetylcholine release through a GABAα receptor-mediated mechanism that was abolished by tetrodotoxin. These results indicate that γ-aminobutyric acid is present in and taken up by epithelial cells of the gastric antrum and that γ-aminobutyric acid is capable of being synthesized by antral mucosal/submucosal tissues. Furthermore, these studies suggest that a peripheral γ-aminobutyric acid mechanism that may modulate cholinergic neurotransmission and endocrine cell function exists within the antrum.