Bicuculline-sensitive gamma-aminobutyrate binding processes in a synaptosome-enriched fraction of rat cerebral cortex.

The binding of low concentrations of [³H]y-aminobutyrate (GABA) to a synaptosomal fraction of rat cerebral, cortex was studied in the presence and absence of added Na⁺; unlabelled GABA and bicuculline methiodide were used to estimate ‘GABA-sensitive’ and ‘bicuculline-sensitive’ binding sites. Significant amounts of [³H]GABA were bound to the particles in both the presence and absence of added Na⁺. In Na⁺-free medium, a single bicuculline-sensitive, high-affinity [³H]GABA binding process was detected, its GABA-sensitive sites having K_B ～- 10^?5M. In Na⁺-containing medium, two bicuculline-sensitive, high-affinity [³H]GABA binding processes were detected, the lower-affinity process having GABA-sensitive sites with K_B ～- 10^?5M and the higher-affinity process having GABA-sensitive sites with K_B ～- 4 × 10^?8MOur findings suggest that bicuculline-sensitive components of [³H]GABA binding in the absence of Na⁺ and in the presence of Na⁺ (higher-affinity process) could represent estimates of Na⁺-indepen dent and Na⁺-dependent synaptic GABA-receptors. The bicuculline-sensitive component of lower-affinity [³H]GABA binding in the presence of Na⁺ might be related to an action of bicuculline on GABA transport. Two GABA-receptor agonists displaced about the same amount of [⁺H]GABA as did bicuculline in Na⁺-free medium, indicating further that a synaptic GABA-receptor was involved in [³H]GABA binding under these conditions. Nipecotic acid markedly inhibited [³H]GABA binding in both the presence and absence of added Na⁺, indicating that some transport sites become occupied by GABA in the absence of added Na⁺ and that nipecotic acid might interact to some extent with synaptic GABA-receptors.