The cannabinoid receptors are a class of receptors within the G-protein coupled receptor superfamily. Their ligands are known as cannabinoids or endocannabinoids depending on whether they come from external or internal (endogenous) sources, respectively (Howlett et al. 2002). Endocannabinoids serve as intercellular lipid messengers, signaling molecules that are released from one cell and activate the cannabinoid receptors present on other cells.
Cannabinoid type 1 (CB1) receptors (Gerrard et al. 1990) are thought to be the most widely expressed G-protein coupled receptors in the brain, lungs, liver and kidneys. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release.
CB2 receptors (Munro et al. 1993) are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. Current research suggests that these receptors play a role in nociception, or the perception of pain.
Both receptors' activity is mediated by coupling to the G protein alpha i/o subunit, which inhibits adenylyl cyclase (Bouaboula et al. 1995, Bayewitch et al. 1995).
GPR55 is activated by plant cannabinoids and the endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide (AEA), leading to suggestions that it should be renamed CB3. However GPR55 has also been reported as a receptor for LPI and its derivative 2-Arachidonoyl-sn-glycero-3-phosphoinositol. 2-AG binds to the CB1 and CB2 receptors with similar affinity, acting as a full agonist.