Evidence that ethylenediamine acts in the isolated ileum of the guinea-pig by releasing endogenous GABA.

Ethylenediamine (EDA) released [3H]-gamma-aminobutyric acid ([3H]-GABA) in a dose-dependent manner from the isolated preloaded ileum of the guinea-pig maintained in Krebs-bicarbonate solution (pH 7.4, 37 degrees C), in the presence of beta-alanine and amino-oxyacetic acid (AOAA) to prevent GABA uptake into glial cells and catabolism. This release was reversibly prevented by 3-mercaptopropionic acid (3-MPA), also in a dose-dependent manner. In the isolated ileal preparations of the guinea-pig maintained in Krebs-bicarbonate solution, EDA induced a dose-dependent transient, cholinergic contractile response (GABAA-receptor-mediated effect), followed by an 'after-relaxation' (GABAB-receptor-mediated effect). EDA also induced a transient contraction superimposed on repetitive twitch responses to electrical transmural stimulation of the cholinergic neurones, followed by a depression of the twitch contractions. This GABAA-receptor-mediated contraction was antagonized by bicuculline methochloride and picrotoxinin, whilst the GABAB-receptor-mediated 'after-relaxation', and depression of cholinergic twitch contractions, was susceptible to antagonism by delta-aminovaleric acid. The pA2 value for bicuculline methochloride antagonism of EDA was estimated to be 5.8, identical with that for GABA. 3-Mercaptopropionic acid also prevented these pharmacological actions induced by EDA without affecting responses to GABA, 3-aminopropranesulphonic acid, muscimol, baclofen or the twitch responses to transmural stimulation. It is concluded that EDA releases both [3H]-GABA and endogenous GABA in the guinea-pig ileum, thus providing further evidence that GABA is a transmitter in the enteric nervous system.