Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum.
A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (Kd = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [3H]CGS 21680. Agonist displacement profile of [3H]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA greater than (R)-PIA greater than CPA greater than (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior.
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002421:Caudate Nucleus / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000502:physiology*; D004285:Dogs; D015723:Gene Library; D007033:Hypothalamus, Middle / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010627:Phenethylamines / Q000378:metabolism; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011699:Putamen / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D011983:Receptors, Purinergic / Q000235:genetics* / Q000378:metabolism; D017385:Sequence Homology; D014162:Transfection
D000959:Antihypertensive Agents; D009838:Oligodeoxyribonucleotides; D010627:Phenethylamines; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D011983:Receptors, Purinergic; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D011061:Poly A; D012313:RNA; D000241:Adenosine