Adenosine A2A Receptors are Colocalized with and Activate Golf in Rat Striatum

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Vol. 58, Issue 4, 771-777, October 2000

Adenosine A_2A Receptors are Colocalized with and Activate G_olf in Rat Striatum

Björn Kull, Per Svenningsson, and Bertil B. Fredholm

Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Karolinska Institutet, Stockholm, Sweden

In situ hybridization with cRNA probes showed A_2A receptor and G_olf mRNAs to be abundantly expressed in caudate putamen, nucleusaccumbens, and olfactory tubercle, whereas G_s mRNA shows a comparativelylow expression in regions expressing A_2A receptors. In caudateputamen, 49% of the medium-sized neuron-like cells exhibited astrong signal for adenosine A_2A receptor mRNA, and 98% showeda strong signal for G_olf mRNA. In contrast, G_s mRNA was foundin only 12% of the medium-sized neuron-like cells in caudate putamen.The coexpression of adenosine A_2A receptor mRNA with that of G_olfor G_s mRNAs was studied with double in situ hybridization. A largemajority (91-95%) of the neurons in caudate-putamen that containedadenosine A_2A receptor mRNA also expressed G_olf mRNA, whereasonly 3 to 5% of the neurons with adenosine A_2A receptor mRNA coexpressedG_s mRNA. The A_2A receptor agonist CGS 21680 [2-[p-(2-carbonylethyl)phenylethylamino-5'-N-ethylcarboxamidoadenosine]dose dependently activated G_olf subunits in striatal membranesas shown by photolabeling with [ $alpha$ -³²P]m-acetylanilido-GTP followed by immunoprecipitation with a specificantibody against G_olf. Transfection of G_olf cDNA into Chinesehamster ovary cells, which stably express human adenosine A_2Areceptors, led to an increased efficacy of CGS 21680, as evidencedby a stronger cAMP response, indicating that activation of G_olfby A_2A receptors leads to a biological signal. In conclusion,these results provide anatomical and biochemical evidence thatadenosine A_2A receptors stimulate G_olf rather than G_s instriatum.

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