A(2) adenosine receptors: Their presence and neuromodulatory role in the central nervous system

1. Adenosine is an endogenous neuromodulator that exerts its depressant effect on neurons by acting on the A(1) adenosine receptor subtype. Excitatory actions of adenosine, mediated by the activation of the A(2) adenosine receptor subtype, have also been shown in the central nervous system. 2. Adenosine A(2a) receptors are highly localized in the striatum, as demonstrated by the binding assay of the A(2a) selective agonist, CGS2680, and by analysis of the A(2) receptor mRNA localization with in situ hybridization histochemistry. However, adenosine A(2a) receptors, albeit at lower levels, are also localized in other brain regions, such as the cortex and the hippocampus. 3. In the striatum, adenosine A(2a), receptors are implicated in the control of motor activity. Evidences exists of an antagonistic interaction between adenosine A(2a) and dopamine D-2 receptors. 4. Utilizing selective agonists and antagonists for adenosine A(2a) receptors, their role in the modulation of the release of several neurotransmitters (acetylcholine, dopamine, glutamate, GABA) has been extensively studied in the brain (striatum, cortex, hippocampus). Controversial results have been obtained and, because the overall effect of endogenous adenosine in the brain is that of an inhibitory tonus, the physiological meaning of the excitatory A(2) receptor remains to be clarified.