Receptor Information

CB1 and CB2 receptors are the members of class A GPCR family, so they share a common structural feature of this class, having an extracellular glycosylated amino N-terminal and an intracellular carboxy C-terminal. The terminals are connected by seven transmembrane (TM) regions, three intracellular (ICL1, ICL2, ICL3) and three extracellular (ECL1, ECL2, ECL3) loops and an amphipathic helix 8. CB2 receptor shows 44% sequence similarity and high degree of homology with CB1. There are 2 highly conserved regions, NPxxY motif and DRY motif, whose residues adopt almost the same position in all the active structures present till now. CB1 and CB2 receptors are coupled to G-proteins,which comprise of α, β, γ subunits. Therefore, they participate in G-protein (Gi/o family) mediated signaling pathways. Structurally different ligands when bind to the receptor can activate different signal transduction pathways, which in turn mediates various downstream signaling cascades. This process termed as “biased signaling” or functional selectivity, can provide therapeutical advantage by targeting a specific pathway to get desired effect. Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in various physiological and pathological conditions. Thus, many efforts are been made to develop ligands for CB1 and CB2 receptors, resulting in number of phyto and synthetic cannabinoids with varying affinities for the treatment of various diseases.