γ-Aminobutyric acid action in guinea-pig ileal myenteric plexus

Abstract

The responses of the guinea-pig ileum myenteric plexus-longitudinal muscle preparation to γ-aminobutyric acid (GABA) and several analogs were examined in direct and electrically stimulated preparations. GABA, muscimol and 3-aminopropane sulfonic acid (3-APS), but not baclofen, produced a transient, concentration-dependent contraction followed by relaxation. These responses were antagonized by atropine, tetrodotoxin, bicuculline methiodide and picrotoxin. Responses to GABA and 3-APS exhibited a marked tachyphylaxis. GABA and baclofen, but not muscimol or 3-APS, exerted a relaxant effect on contractions induced by supramaximal field stimulation in the longitudinal muscle. These responses were insensitive to bicuculline, bicuculline methiodide and picrotoxin, and were unaffected by other pharmacological agents including adrenergic, cholinergic and histamine antagonists. The results suggest that GABA and its analogs act at a population of excitatory receptors mediating the release of acetylcholine from enteric neurons, and at a population of inhibitory receptors which inhibit the stimulated release of acetylcholine.