Benzodiazepine receptors in human brain: characterization, subcellular localization and solubilization

1. Benzodiazepine receptors have been characterized in human brain mainly using 3H]-Ro 15-1788 and 3H]-flunitrazepam. Both ligands present a very high affinity for the receptor sites (Kd values of 0.56 and 1.53 nM respectively). 2. GABA enhanced the affinity of 3H]-flunitrazepam and 3H]-diazepam, but not that of 3H]-Ro 15-1788 and 3H]-methyl-beta-carboline 3-carboxylate for their specific binding sites as well in cerebral as in cerebellar human cortex. 3. Subcellular distribution of the benzodiazepine receptors revealed a main synaptosomal localization in human cerebral cortex, cerebellum and striatum. 4. Solubilized benzodiazepine receptors were obtained using 0.5% sodium deoxycholate and were characterized with 3H]-Ro 15-1788. The solubilized receptors are still coupled to GABA receptors since the 3H]-flunitrazepam specific binding was enhanced in the presence of micromolar concentrations of GABA.