Chimeric D2/D3 dopamine receptor coupling to adenylyl cyclase.

We have sought to determine which area of the D2 dopamine receptor's third intracellular loop contributes to G-protein coupling by constructing reciprocal chimeric D2/D3 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 D2/D3 receptor chimeras were able to effectively inhibit adenylyl cyclase activity to almost the same extent as that seen with the D2 receptor whereas the D3 receptor was without effect. These results suggest that the D2 receptor possesses two redundant and independent domains for G-protein coupling and inhibition of adenylyl cyclase activity.