Quantitative autoradiography of 4'-ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate binding to the GABAA receptor complex.

4'-Ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate ([3H]EBOB) binding to the GABAA receptor complex was characterized autoradiographically in rat brain and then its binding in human brain was investigated. [3H]EBOB binding was saturable, specific and identified a single population of binding sites. The Kd obtained from saturation studies was 4.59 nM. Picrotoxin produced dose-dependent inhibition of [3H]EBOB binding and saturation analysis indicated a competitive interaction. Isoguvacine inhibited [3H]EBOB binding with regionally different effects. Bicuculline increased [3H]EBOB binding only in the cerebellar granule cell layer. In human cerebellum, a high level of [3H]EBOB binding sites was seen in the granule cell layer. These results suggest that [3H]EBOB binds to the picrotoxin binding site associated with the GABAA receptor complex, that regional differences in GABAA agonist and antagonist modulation of [3H]EBOB binding reflect underlying regional differences in GABAA receptor subunit composition, and that there is a species difference in GABAA receptor distribution between human and rat cerebellum.