Influence of GABA and ethylenediamine in the guinea-pig duodenum

1. GABA induced concentration-dependent transient contractions of the guinea-pig duodenum, but only occasionally evoked small relaxatory responses. The GABA-induced contractions were blocked by atropine and tetrodotoxin but were not influenced by hexamethonium; during electrically evoked twitch contractions, GABA had a concentration-dependent inhibitory effect. 2. The concentration-response curve for the contractile effect of GABA was shifted to the right in a dose-dependent manner by bicuculline and picrotoxin, with a clear reduction of the maximal effect in the presence of picrotoxin. 3. Homotaurine and delta-aminovaleric acid but not baclofen mimicked the GABA-induced contractions; the responses induced by these GABAA receptor agonists were antagonized by atropine, tetrodotoxin and bicuculline. Baclofen concentration-dependently inhibited electrically evoked twitch contractions. 4. Ethylenediamine also had a GABA-like effect, and cross-desensitization developed between GABA and ethylenediamine. 5. The ethylenediamine-induced contractions were not antagonized by thiosemicarbazide; they were reduced by 3-mercaptopropionic acid but the GABA-induced contractions were reduced to the same extent. 6. It is concluded that GABA induces contraction of the guinea-pig duodenum by excitation of GABAA receptors on postganglionic cholinergic neurones; a GABAB receptor-mediated inhibitory effect can be observed during electrically evoked twitch contractions. Ethylenediamine mimicks the GABAA receptor-mediated effect probably by a direct effect on the GABAA receptors.