Distribution, biochemistry and function of striatal adenosine A2A receptors.
It is well known that the nucleoside adenosine exerts a modulatory influence in the central nervous system by activating G protein coupled receptors. Adenosine A2A receptors, the subject of the present review, are predominantly expressed in striatum, the major area of the basal ganglia. Activation of A2A receptors interferes with effects mediated by most of the principal neurotransmitters in striatum. In particular, the inhibitory interactions between adenosine acting on A2A receptors and dopamine acting on D2 receptors have been well examined and there is much evidence that A2A 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 A2A receptors has increased dramatically over the last few years. New selective antibodies, antagonist radioligands and optimized in situ hybridization protocols have provided detailed information on the distribution of A2A receptors in rodent as well as primate striatum. Studies on the involvement of A2A receptors in the regulation of DARPP-32 and the expression of immediate early genes, such as nerve growth factor-induced clone A and c-fos, have pointed out an important role for these receptors in regulating striatopallidal neurotransmission. Moreover, by using novel selective antagonists for A2A receptors and transgenic mice lacking functional A2A receptors, crucial information on the behavioral role of striatal A2A receptors has been provided, especially concerning their involvement in the stimulatory action of caffeine and the anti-Parkinsonian properties of A2A receptor antagonists. In the present review, current knowledge on the distribution, biochemistry and function of striatal A2A receptors is summarized.
Svenningsson
P
P
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Le Moine
C
C
Fisone
G
G
Fredholm
B B
BB
D000818:Animals; D017072:Neostriatum / Q000737:chemistry* / Q000502:physiology; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000737:chemistry* / Q000502:physiology
D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1