We have demonstrated that D-5 and D-2 dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D-5 receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D-2 receptor two adjacent arginine residues. Any pairing of these three D-5 receptor glutamic acids were sufficient for heteromer formation. These identified residues in D-5 and D-2 receptors are oppositely charged and likely interact by electrostatic interactions. (C) 2013 Elsevier Inc. All rights reserved.