Quantitative autoradiography of [formula omitted] binding to the GABA A receptor complex

Abstract

4′- Ethynyl-4-n-[2,3- 3 H 2] propylbicycloorthobenzoate ([ 3H]EBOB) binding to the GABA A 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 K d obtained from saturation was 4.59 nM. Picrotoxin produced dose-dependent inhibition of [ 3H]EBOB binding and saturation analysis indicated a competetitive 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 GABA A receptor complex, that regional differences in GABA A agonist and antagonist modulation of [ 3H]EBOB binding reflect underlying regional differences in GABA A receptor subunit composition, and that there is a species difference in GABA A receptor distribution between human and rat cerebellum.