title: Functional expression of single-chain heterodimeric G-protein-coupled receptors for adenosine and dopamine.
abstract: The direct homo- and heteromeric association between G-protein-coupled receptors (GPCRs), adenosine A2A receptor (A(2A)R) and dopamine D2 receptor (D2R), occurs although little is known about the selectivity of their formation (A(2A)R/A(2A)R vs. A(2A)R/D2R). In order to stimulate the heteromerization of A(2A)R and D2R, we have designed a single-polypeptide-chain heterodimeric A(2A)R/D2R complex by fusing the C-terminus of the A(2A)R via transmembrane (TM) of a type II TM protein with the N-terminus of D2R in tandem. This was successfully expressed on the cell surface as a full-length protein with specific binding to the respective ligands and functional coupling to G-proteins comparable to wild-type receptors, suggesting the possible creation of physiologically relevant heteromeric A(2A)R/D2R. This expression system would be useful to exclusively clarify the properties of heteromeric GPCRs irrespective of homomeric receptors.
authors.affiliation: Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kamiya
authors.forename: Osamu
authors.initials: O
authors.lastname: Saitoh
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakata
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D019281:Dimerization; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D010627:Phenethylamines / Q000494:pharmacology; D011485:Protein Binding; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D019257:Quinpirole / Q000494:pharmacology; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000737:chemistry* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
chemical_list: D018491:Dopamine Agonists; D008024:Ligands; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D005576:Colforsin; D019257:Quinpirole; D000242:Cyclic AMP; D000241:Adenosine