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FEBS Lett. 2002 Jul 3;522(1-3):130-4.

Role of intracellular loops of cannabinoid CB(1) receptor in functional interaction with G(alpha16).

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Department of Pharmacology, Physiology and Therapeutics, University of North Dakota, Grand Forks 58202, USA.


The cannabinoid CB(1) but not the CB(2) receptor was demonstrated to couple via G(alpha16) to activate phospholipase C after co-expression in COS7 cells. Chimeric CB(1)/CB(2) 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 CB(1) into the CB(2) receptor. Only the triple mutant with all three regions replaced activated phospholipase C to a similar extent as the CB(1) 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.

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