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

Abstract
The cannabinoid CB1 but not the CB2 receptor was demonstrated to couple via Gα16 to activate phospholipase C after co-expression in COS7 cells. Chimeric CB1/CB2 receptors were used as a model to study receptor–Gα16 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 Gα16. Several sub-domains within the third intracellular loop were identified for receptor–Gα16 interaction