Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D-2, and Adenosine A(2A) G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

Functional interactions in signaling occur between dopamine D-2 (D2R) and cannabinoid CB1 (CB1R) receptors, between CB1R and adenosine A(2)A (A(2)AR) receptors, and between D2R and A(2)AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A(2)AR- D2R, and CB1R-A(2)AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A(2)AR hetero-oligomers in living cells.