Bicuculline-insensitive GABA receptors: studies on the binding of (-)-baclofen to rat cerebellar membranes.

The binding of [3H](-)-baclofen to synaptic membranes prepared from rat cerebellum was studied. Consistent with pharmacological data that (-)-baclofen is the more active stereoisomer, studies on the binding of [3H](-)-baclofen showed increased specific binding, a higher affinity Kd and a lower Bmax than equivalent studies using [3H](+/-)-baclofen. Divalent metal ions (mercury, lead, calcium and zinc) inhibited the binding of [3H](-)-baclofen. The effects of some conformationally restricted analogues of gamma-aminobutyric acid (GABA) on [3H](-)-baclofen binding indicated that GABA interacts with (-)-baclofen-sensitive binding sites (GABAB) in extended rather than folded conformations, and that folded analogues of GABA may interact with a class of binding site (GABAc?) insensitive to (-)-baclofen and bicuculline.