Abstract
In situ hybridization with cRNA probes showed A2A receptor and Golf mRNAs to be abundantly expressed in caudate putamen, nucleus accumbens, and olfactory tubercle, whereas Gs mRNA shows a comparatively low expression in regions expressing A2A receptors. In caudate putamen, 49% of the medium-sized neuron-like cells exhibited a strong signal for adenosine A2A receptor mRNA, and 98% showed a strong signal for Golf mRNA. In contrast, Gs mRNA was found in only 12% of the medium-sized neuron-like cells in caudate putamen. The coexpression of adenosine A2A receptor mRNA with that of Golf or Gs mRNAs was studied with double in situ hybridization. A large majority (91–95%) of the neurons in caudate-putamen that contained adenosine A2A receptor mRNA also expressed Golf mRNA, whereas only 3 to 5% of the neurons with adenosine A2A receptor mRNA coexpressed Gs mRNA. The A2A receptor agonist CGS 21680 [2-[p-(2-carbonylethyl)phenylethylamino-5′-N-ethylcarboxamidoadenosine] dose dependently activated Golf subunits in striatal membranes as shown by photolabeling with [α-32P]m-acetylanilido-GTP followed by immunoprecipitation with a specific antibody against Golf. Transfection of Golf cDNA into Chinese hamster ovary cells, which stably express human adenosine A2A receptors, led to an increased efficacy of CGS 21680, as evidenced by a stronger cAMP response, indicating that activation of Golf by A2A receptors leads to a biological signal. In conclusion, these results provide anatomical and biochemical evidence that adenosine A2A receptors stimulate Golf rather than Gs in striatum.
Footnotes
- Received December 29, 1999.
- Accepted July 26, 2000.
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Send reprint requests to: Dr. Björn Kull, Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail:bjorn.kull{at}fyfa.ki.se
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These studies were supported by the Swedish Medical Research Council (proj no. 2553), by Knut and Alice Wallenberg's Foundation, and Karolinska Institutet.
- The American Society for Pharmacology and Experimental Therapeutics
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