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.