Cannabinoid receptor homo- and heterodimerization

CB1 cannabinoid receptors mediate the psychoactive effects of Delta(9)THC and actions of the endogenous cannabinoids [Howlett, A.C., Barth, F., Bonner, T.I., Cabral, G., Casellas, P., Devane, W.A., Felder, C.C., Herkenham, M., Mackie, K., Martin, B.R., Mechoulam, R., Pertwee, R.G., 2002. International Union of Pharmacology: XXVII. Classification of cannabinoid receptors. Pharmacological Reviews 54 (2) 161-202.]. CBl receptors belong to the G protein-coupled receptor (GPCR) superfamily. In recent years, it has become apparent that many GPCRs exist as multimers-either of like or unlike receptors [Kroeger, K.M., Pfleger, K.D., Eidne, K.A., 2003. G-protein coupled receptor oligomerization in neuroendocrine pathways. Frontiers of Neuroendocrinology 24 (4) 254-278; Milligan, G., 2004. G protein-coupled receptor dimerization: function and ligand pharmacology. Molecular Pharmacology 66 (1) 1-7.]. Importantly, GPCR multimerization plays a key role in enriching the signaling repertoire of these receptors. In this review, the evidence for CB I multimerization will be presented, the implications for cannabinoid signaling discussed, and possible future directions for this research considered. (c) 2005 Elsevier Inc. All rights reserved.