Abstract

The action of gamma-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 (IC50 4 micro M) and reduced the twitch responses of the vas deferens (IC50 3 micro M) in a dose-dependent manner. These depressant effects were not prevented by recognized GABA antagonists such as bicuculline and picrotoxin. Numerous GABA analogues, in particular 3-aminopropanesulphonic acid, failed to mimic the action of GABA. However, beta-p-chlorophenyl GABA (baclofen) was stereospecifically active. Other related beta-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.