CHARACTERIZATION OF PERIPHERAL-TYPE BENZODIAZEPINE BINDING-SITES IN BRAIN USING (H-3)-LABELED RO-5-4864

Abstract

The binding of [3H]Ro 5-4864 to the peripheral-type benzodiazepine binding site in [rat] brain was characterized. The binding was saturable, high-affinity (Kd = 1.6 nM) and reversible. The comparison of [3H]Ro 5-4864 and [3H]diazepam binding sites revealed major differences which include the following. There were .apprx. 1/4 as many peripheral-type binding sites than central sites in brain. Peripheral sites are present in many extranervous tissues and have a brain regional distribution distinct from that of the central-type receptor. The [3H]Ro 5-4864 binding site is apparently highly localized in the nuclear membrane in contrast to the central-type receptor, which is synaptosomal. GABA had no effect on [3H]Ro 5-4864 binding, again in contrast to its marked effect on [3H]diazepam binding. Various putative benzodiazepine receptor ligands, such as purines, .beta.-carbolines and kynurenamines are also inactive as inhibitors of [3H]Ro 5-4864 binding. Blocking the benzodiazepine receptor by photoaffinity labeling decreases [3H]diazepam binding by > 80% and has no effect on [3H]Ro 5-4864 binding. The peripheral-type benzodiazepine binding site in brain is apparently a separate entity whose physiological function is probably distinct from that of the central-type benzodiazepine receptor.