gamma-Aminobutyric acid stimulates intrinsic inhibitory and excitatory nerves in the guinea-pig intestine.

The sites of action of gamma-aminobutyric acid (GABA) were examined in preparations of the distal colon and ileum of guinea pigs. GABA caused transient relaxations of the longitudinal and circular muscle of the colon and transient contractions followed by relaxation of the muscle of the ileum. The responses of both parts of the intestine were antagonized by tetrodotoxin and by bicuculline. Nerve-free preparations of the longitudinal muscle of the ileum were not affected by GABA, even in concentrations up to 10(-4) g/ml. There was a marked tachyphylaxis of the responses to GABA. Relaxations in response to GABA were not affected by pentolinium or by a combination of phentolamine and propranolol. Contractions in response to GABA were blocked by hyoscine. Neither the ascending excitatory or descending inhibitory components of the peristaltic reflex in the distal colon were affected by bicuculline or by making the intestine tachyphylactic to GABA. The results indicate that GABA stimulates receptors mediating excitation of cholinergic excitatory and enteric inhibitory neurons whereas it has little or no direct effect on the muscle of the ileum or distal colon.