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

1 Ethylenediamine (EDA) released [ 3 H]‐γ‐aminobutyric acid ([ 3 H]‐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 (GABA A ‐receptor‐mediated effect), followed by an ‘after‐relaxation’ (GABA B ‐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 GABA A ‐receptor‐mediated contraction was antagonized by bicuculline methochloride and picrotoxinin, whilst the GABA B ‐receptor‐mediated ‘after‐relaxation’, and depression of cholinergic twitch contractions, was susceptible to antagonism by δ‐aminovaleric acid. The pA 2 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 [ 3 H]‐GABA and endogenous GABA in the guinea‐pig ileum, thus providing further evidence that GABA is a transmitter in the enteric nervous system.