ALPHA(2)-ADRENOCEPTOR SUBTYPES IN THE HUMAN BRAIN - A PHARMACOLOGICALDELINEATION OF [H-3] RX-821002 BINDING TO MEMBRANES AND TISSUE-SECTIONS

In order to study the characterization and localization of [H-3]RX-821 002 (2-methoxy-idazoxan) binding to alpha(2)-adrenoceptor subtypes in several regions of the human brain, we have carried out competition st udies using both autoradiography and membrane binding assays. The alph a(2A)-adrenoceptor subtype was found to be predominant in the differen t layers of the frontal cortex, cerebellum and hippocampal formation, while in the neostriatum it was the non-alpha(2A)- (alpha(2B)- and alp ha(2C)-) adrenoceptor subtype. In the frontal cortex, in addition to b inding to the alpha(2A)-adrenoceptor subtype, [H-3]RX-821002 bound als o to a small portion of alpha(2B)- and alpha(2C)-adrenoceptors in laye r III, and labelled in the dentate gyrus and the CA(1) field, together with 5-HT1A receptors. 5-HT1A receptors were labelled predominantly i n the stratum pyramidale layer. These results, in addition to delineat e the relative presence of alpha(2)-adrenoceptor subtypes, indicate th at caution is needed when analyzing RX 821002 binding to human brain t issue.