Chimeric D2/D3Dopamine Receptor Coupling to Adenylyl Cyclase☆

Abstract We have sought to determine which area of the D 2 dopamine receptor's third intracellular loop contributes to G-protein coupling by constructing reciprocal chimeric D 2 /D 3 receptors with fusion points near the center of the third intracellular loop. Both receptor chimeras were expressed equally well in Chinese Hamster Ovary (CHO) cells and exhibited ligand binding properties similar to those of the wild type receptors. Surprisingly, both of the D 2 /D 3 receptor chimeras were able to effectively inhibit adenylyl cyclase activity to almost the same extent as that seen with the D 2 receptor whereas the D 3 receptor was without effect. These results suggest that the D 2 receptor possesses two redundant and independent domains for G-protein coupling and inhibition of adenylyl cyclase activity.