We investigated whether oligomerization of adenosine A(2A) receptor (A(2A)R) and dopamine D-2 receptor (D2R) exists in living cells using modified bioluminescence resonance energy transfer (BRET2) technology. Fusion of these receptors to a donor, Renilla luciferase (Rluc), and to an acceptor, modified green fluorescent protein (GFP(2)), did not affect the ligand binding affinity, subcellular distribution, and coimmunoprecipitation of the receptors. BRET was detected not only between Myc-D2R-Rluc and A(2A)R-GFP(2) but also between HA-tagged A(2A)R-Rluc and A(2A)R-GFP(2). These results indicate A(2A)R, either homomeric or heteromeric with D,R, exists as an oligomer in living cells. (C) 2003 Elsevier Science (USA). All rights reserved.