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) mRNAs to be abundantly expressed in caudate putamen, nucleus accumbens, and olfactory 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) receptor 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 caudate 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 adenosine A(2A) receptor mRNA also expressed G(olf) mRNA, whereas only 3 to 5% of the 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-ethylcarboxa midoadenosin e] dose dependently activated G(olf) subunits in striatal membranes as shown by photolabeling with [alpha-(32)P]m-acetylanilido-GTP followed by immunoprecipitation with a specific antibody against G(olf). Transfection of G(olf) cDNA into Chinese hamster ovary cells, which stably express human adenosine A(2A) receptors, led to an increased efficacy of CGS 21680, as evidenced by a stronger cAMP response, indicating that activation of G(olf) by A(2A) receptors leads to a biological signal. In conclusion, these results provide anatomical and biochemical evidence that adenosine A(2A) receptors stimulate G(olf) rather than G(s) in striatum.
Kull
B
B
Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Karolinska Institutet, Stockholm, Sweden.
Svenningsson
P
P
Fredholm
B B
BB
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016548:Prosencephalon / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*
D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C084618:olfactory G protein subunit alpha olf; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins