Elimination of palmitoylation sites in the human dopamine D-1 receptor does not affect receptor-G protein interaction

We have eliminated putative palmitoylation sites in the carboxyl tail of the human dopamine D-1 receptor by replacing the two cysteine residues with alanines either separately or together. The wild type and the three mutated dopamine D-1 receptors were stably expressed in baby hamster kidney cells and characterized to detect any resulting alterations in receptor-G protein interactions. The three mutant dopamine D-1 receptors retained the same proportion of high affinity state for agonists as wild type receptors and also no difference was observed in the stimulation of adenylyl cyclase activity. Our results are in contrast to those observed with the beta(2)-adrenoceptor and consistent with similar studies of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors, alpha(2)-adrenoceptors, muscarinic M-2 receptors and thyrotropin releasing hormone (TRH) receptors. Thus, we suggest that palmitoylation appears to play a unique role in the beta(2)-adrenoceptors, and appears not to be essential in G protein coupling for the dopamine D-1 receptors. (C) 1997 Elsevier Science B.V.