Adenosine A2a receptor expression in striatal neurons: Implications for basal ganglia pathophysiology

Two dog adenosine receptors have been recently cloned. They were pharmacologically characterized as an A₁ and the A_2a receptor, respectively. The adenosine A_2a receptor is exclusively expressed in medium-sized neurons of the striatum as demonstrated by in situ hybridization. The relationships of this A_2a receptor with three major components of the striatum, enkephalin, substance P, and choline acetyltransferase, were studied in the rat. This demonstrates that the adenosine A_2a receptor is exclusively expressed by the enkephalinergic striatal neuronal subpopulation that also selectively expresses the dopamine D2 receptor. Conversely, The A_2a receptor is never detected in the substance P containing neurons or in the cholinergic neurons. This observation most probably constitutes the anatomical substratum for the preciously described A_2a-D2 receptors interactions. It also indicates that A_2a receptor is selectively express in the indirect pathway of the basal ganglia system which is hypoactive in hyperkinetic disorders such as Huntington's disease and hyperactive in hypokinetic disorders such as Parkinson's disease. The development of highly A_2a selective ligands could be therefore useful in the therapy useful in the therapy of basal ganglia degenerative diseases. © 1993 Wiley-Liss, Inc.