Role of intracellular loops of cannabinoid CB1 receptor in functional interaction with Gα16

The cannabinoid CB1 but not the CB2 receptor was demonstrated to couple via G(alpha16) to activate phospholipase C after co-expression in COS7 cells. Chimeric CB1/CB2 receptors were used as a model to study receptor-G(alpha16) interaction. Sequences of the second and third intracellular loops and the carboxy-terminus were substituted from the CB1 into the CB2 receptor. Only the triple mutant with all three regions replaced activated phospholipase C to a similar extent as the CB1 receptor, suggesting that all three intracellular regions are required for interacting with G(alpha16). Several sub-domains within the third intracellular loop were identified for receptor-G(alpha16) interaction. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.