Action of N-methyl-bicuculline on the binding of γ-aminobutyric acid to a synaptosomal fraction of rat cerebral cortex

Abstract

The interaction of N-methyl-bicuculline and γ-aminobutyric acid (GABA) on a synaptosomal fraction of rat cerebral cortex was examined at 0 C in a balanced bicarbonate-buffered medium using differential centrifugation and double-isotope scintillation spectrometry. The drug, at 10 −4 m, produced a significant decrease in the binding of [ 3H]GABA (10 −8, 10 −7 m) to the particles. Further experiments revealed that N-methyl-bicuculline, at concentrations of 10 −7–10 −3 m, significantly decreased the “binding” of GABA (4.8 × 10 −8 m) to the particles. This bicuculline-induced reduction in GABA binding exhibited linear characteristics over a 10 −10–10 −3 m concentration range of the drug, and when present at 10 −3 m, the drug decreased GABA binding by about 23%. This demonstration of a bicuculline-sensitive component of GABA binding to synaptosomal particles adds support to neurophysiological studies which have indicated that bicuculline may serve as an antagonist to the GABA receptor in vivo.