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lüll Ligand- and heterodimer-directed signaling of the CB(1) cannabinoid receptor Hudson BD; Hebert TE; Kelly MEMol Pharmacol 2010[Jan]; 77 (1): 1-9Seven-transmembrane G protein-coupled receptors (GPCRs) represent the single largest family of cell surface receptors. Signaling through these receptors is controlled by changes in the conformation of the receptor from inactive to active conformations, which in turn lead to the activation of multiple downstream signaling pathways. To facilitate greater diversity in signaling responses, many of these receptors are capable of adopting several distinct active conformations, in which each couples preferentially to its own set of downstream signaling partners. Because these unique signaling responses result from specific receptor active conformations, GPCR signaling may be directed toward these selective responses through either strength-of-signal effects resulting from partial agonism or through biased agonism and functional selectivity, resulting from the selective stabilization of one active conformation over the others. This review uses the CB(1) cannabinoid receptor as a specific example to highlight the contribution of two important aspects of GPCR function-orthosteric ligand binding and receptor heterodimerization-toward directed GPCR signaling.|*Signal Transduction[MESH]|Humans[MESH]|Ligands[MESH]|Protein Multimerization[MESH]|Receptor, Cannabinoid, CB1/chemistry/*metabolism[MESH]|Receptors, G-Protein-Coupled/chemistry/metabolism[MESH] |