γ-Aminobutyric acid activation of 36Cl-flux in rat hippocampal slices and its potentiation by barbiturates

Abstract

γ-Aminobutyric acid (GABA) increases the rate of 36Cl- efflux from preloaded rat hippocampal slices in a dose-dependent manner (EC 50: 400 μM). This action has the pharmacological specificity expected of activation of GABA receptor in that it is mimicked by the agonists muscimol and 3-aminopropanesulfonic acid, and blocked by the antagonists bicuculline and picrotoxinin. GABA uptake inhibitors, nipecotic acid and 2, 4-diaminobutyric acid, fail to increase 36Cl- flux. Pentobarbital produces a dose-dependent activation (EC 50 = 1.5mM) of 36Cl- efflux with maximal response greater than that of GABA. The effect of pentobarbital can be mimicked by 1, 3-dimethylbutylbarbiturate, secobarbital, (+)hexobarbital but not (−)hexobarbital, and is blocked by bicuculline and picrotoxinin. Pentobarbital and the other active barbiturates also potentiate the action of GABA. Phenobarbital does not have any effect independently or in combination with GABA. It is suggested that GABA increases 36Cl- permeability by activation of a postsynaptic receptor which is in turn functionally copupled to a barbiturate receptor.