Biochemical identification of multiple GABAB binding sites: association with noradrenergic terminals in rat forebrain.

GABAA (bicuculline-sensitive) and GABAB (bicuculline-insensitive) receptor binding were examined in an attempt to determine whether either site was present on noradrenergic terminals in rat brain cerebral cortex. Equilibrium binding saturation studies revealed the presence of two GABAB binding sites in brain tissue, with affinity constants of 60 and 229 nM. Regional distribution studies in the cow brain revealed that the ratio of the high and low affinity GABAB binding sites differed among the areas examined. Both GABAA and GABAB binding were examined in the rat brain cortex 12 days following a unilateral lesion of the dorsal noradrenergic bundle. While GABAA and high affinity GABAB binding were unaffected by the lesion, the number of low affinity GABAB sites was significantly reduced. These results indicate that high and low affinity GABAB binding sites may be anatomically distinct, with only the latter being associated with cerebral cortical noradrenergic nerve terminals.