Functional evidence for different roles of GABA(A) and GABA(B) receptors in modulating mouse gastric tone.

Abstract

The aims of the present study were to investigate, using mouse whole stomach in vitro, the effects of g-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABAA-receptor antagonist, bicuculline, potentiated by phaclofen, GABAB-receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin- 4-yl methylphosphinic acid hydrate (TPMPA), GABAC-receptor antagonist. Muscimol, GABAA-receptor agonist, mimicked GABA effects inducing relaxation, which was significantly reduced by bicuculline, Nu-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthase or apamin, inhibitor of small conductance Ca2þ-dependent Kþ channels, which blocks the purinergic transmission in this preparation. It was abolished by tetrodotoxin (TTX) or L-NAME plus apamin. Baclofen, a specific GABABreceptor agonist, induced an increase in the gastric tone, which was antagonized by phaclofen and abolished by TTX or atropine. Bicuculline, but not phaclofen or TPMPA, per se induced an increase in gastric tone, which was prevented by L-NAME. In conclusion, our results suggest that GABA is involved in the regulation of mouse gastric tone, through modulation of intrinsic neurons. Activation of GABAAreceptors mediates relaxation through neural release of NO and neurotransmitters, activating Ca2þ- dependent Kþ channels, likely purines, while activation of GABAB-receptors leads to contraction through acetylcholine release.