Adenosine A(2A) receptors are colocalized with and activate G(olf) in rat striatum

In situ hybridization with cRNA probes showed A(2A) receptor and G(olf) mRN As to be abundantly expressed in caudate putamen, nucleus accumbens, and ol factory tubercle, whereas G(s) mRNA shows a comparatively low expression in regions expressing A(2A) receptors. In caudate putamen, 49% of the medium- sized neuron-like cells exhibited a strong signal for adenosine A(2A) recep tor mRNA, and 98% showed a strong signal for G(olf) mRNA. In contrast, G(s) mRNA was found in only 12% of the medium-sized neuron-like cells in caudat e putamen. The coexpression of adenosine A(2A) receptor mRNA with that of G (olf) or G(s) mRNAs was studied with double in situ hybridization. A large majority (91-95%) of the neurons in caudate-putamen that contained adenosin e A(2A) receptor mRNA also expressed G(olf) mRNA, whereas only 3 to 5% of t he neurons with adenosine A(2A) receptor mRNA coexpressed G(s) mRNA. The A( 2A) receptor agonist CGS 21680 [2-[p-(2-carbonylethyl) phenylethylamino-5'- N-ethylcarboxamidoadenosine] dose dependently activated Golf subunits in st riatal membranes as shown by photolabeling with [ alpha-P-32]m-acetylanilid o-GTP followed by immunoprecipitation with a specific antibody against G(ol f). Transfection of G(olf) cDNA into Chinese hamster ovary cells, which sta bly express human adenosine A(2A) receptors, led to an increased efficacy o f CGS 21680, as evidenced by a stronger cAMP response, indicating that acti vation of G(olf) by A(2A) receptors leads to a biological signal. In conclu sion, these results provide anatomical and biochemical evidence that adenos ine A(2A) receptors stimulate G(olf) rather than G(s) in striatum.