BICUCULLINE-SENSITIVE GAMMA-AMINOBUTYRATE BINDING PROCESSES IN A SYNAPTOSOME-ENRICHED FRACTION OF RAT CEREBRAL-CORTEX

The binding of low concentrations of [3H].gamma.-aminobutyrate (GABA) to a synaptosomal fraction of rat cerebral cortex was studied in the presence and absence of added Na+; unlabeled 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 KB .simeq. 10-5 M. In Na+-containing medium, 2 bicuculline-sensitive, high-affinity [3H]GABA binding processes were detected, the lower-affinity process having GABA-sensitive sites with KB .simeq. 10-5 M and the higher-affinity process having GABA-sensitive sites with KB .simeq. 4 .times. 10-8 M. 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+-independent 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 [3H]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 and 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.