Distribution, biochemistry and function of striatal adenosine A(2A) receptors

It is well known that the nucleoside adenosine exerts a modulatory influenc e in the central nervous system by activating G protein coupled receptors. Adenosine A(2A) receptors, the subject of the present review, are predomina ntly expressed in striatum, the major area of the basal ganglia. Activation of A(2A) receptors interferes with effects mediated by most of t he principal neurotransmitters in striatum. In particular, the inhibitory i nteractions between adenosine acting on A(2A) receptors and dopamine acting on D-2 receptors have been well examined and there is much evidence that A (2A) receptors may be a possible target for future development of drugs for treatment of Parkinson's disease, schizophrenia and affective disorders. Our understanding of the role of striatal A(2A) receptors has increased dra matically over the last few years. New selective antibodies, antagonist rad ioligands and optimized in situ hybridization protocols have provided detai led information on the distribution of A(2A) receptors in rodent as well as primate striatum. Studies on the involvement of A(2A) receptors in the regulation of DARPP-32 and the expression of immediate early genes, such as nerve growth factor-i nduced clone A and c-Sos, have pointed out an important role for these rece ptors in regulating striatopallidal neurotransmission. Moreover, by using novel selective antagonists for A(2A) receptors and tran sgenic mice lacking functional A(2A) receptors, crucial information on the behavioral role of striatal A(2A) receptors has been provided, especially c oncerning their involvement in the stimulatory action of caffeine and the a nti-Parkinsonian properties of A(2A) receptor antagonists. In the present review, current knowledge on the distribution, biochemistry and function of striatal A(2A) receptors is summarized. (C) 1999 Elsevier S cience Ltd. All rights reserved.