Demonstration of α1A-and α1B-adrenoceptor binding sites in human brain tissue

Abstract

Radioligand binding studies suggest that α 1-adrenoceptor recognition sites are heterogeneous. Several adrenergic agents discriminate between two adrenoceptor binding sites designated α 1A and α 1B. In the present study we demonstrate for the first time that these two subtypes exist in the human brain. 5-Methyl-urapidil and (+)-niguldipine, which have previously been shown to be α 1A-selective, inhibited [ 3H]prazonin binding to cortical membranes in a biphasic manner. The irreversible α 1B-ligand, chloroethylclonidine, preferentially elimanated the binding sites with low affinity for (+)-niguldipine. In contrast, BE 2254 and unlabelled prazosin displaced the radioligand ina monophasic manner. The IC 50 values for prazosin were not affected by pretreatment of the membranes with chloroethylclonidine. Our data on human brain membranes are in excellent agreement with recent findings in rat tissues and suggest that the α 1-adrenoceptor subtypes in human brain are similar to those in rat tissues.