Molecular Biology of Cannabinoid Receptors: Mutational Analyses of the CB Receptors

Abstract

Two cannabinoid receptors have been isolated by molecular cloning; there is also evidence for additional cannabinoid receptor subtypes. The CB1 and CB2 cannabinoid receptors are members of the G-protein coupled receptor (GPCR) superfamily that can be activated by plant-derived, synthetic, and endogenous cannabinoid ligands, which fall into five structurally diverse classes. Studies using mutagenesis and molecular modeling have identified key amino acid residues involved in the selective recognition, activation, desensiti- zation, and internalization of these ligands. The CB1 and CB2 receptors genetic structures indicate polymorphisms and multiple exons that may be involved in tissue- and species-specific regulation of these genes. Polymorphisms in the CB1 and CB2 receptors are associated with drug abuse and disease. Finally, the identification of GPR55 as another GPCR that responds to a diverse set of cannabinoids may herald a new era of molecular biology of cannabinoid receptors.