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

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Abstract
1 Ethylenediamine (EDA) released [3H]-γ-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°C), in the presence of β-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. 2 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. 3 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 δ-aminovaleric acid. The pA2 value for bicuculline methochloride antagonism of EDA was estimated to be 5.8, identical with that for GABA. 4 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. 5 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.