Bicuculline-insensitive gaba receptors on peripheral autonomic nerve terminals

The action of γ-aminobutyric acid (GABA) and related compounds on rat isolated atria and mouse and guinea-pig isolated vas deferens has been studied. GABA depressed the evoked but not basal release of [ 3H]noradrenaline from atria (IC 50 4 μM) and reduced the twitch responses of the vas deferens (IC 50 3 μM) in a dose-dependent manner. These depressant effects were not prevented by recognised GABA antagonists such as bicuculline and picrotoxin. Numerous GABA analogues, in particular 3-aminopropanesulphonic acid, failed to mimic the action of GABA. However, β-p-chlorophenyl GABA (baclofen) was stereospecifically active. Other related β-substituted derivatives were also active but to a lesser degree than GABA. Pretreatment of the vas deferens with the neuronal GABA uptake inhibitors 2,4-diaminobutyric acid or cis-3-aminocyclohexanecarboxylic acid potentiated the action of GABA. These data suggest the presence of a bicuculline-insensitive GABA receptor on autonomic nerve terminals. Preliminary observations indicate a lack of chloride ion dependence in the action of GABA at this site.