Cannabinoid Receptor

Cannabinoid Receptor

The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands, endocannabinoids (produced by the mammalian body), plant cannabinoids (such as THC, produced by the cannabis plant) and synthetic cannabinoids (such as HU-210). All of the endocannabinoids and plant cannabinoids are lipophilic, i.e. fat soluble, compounds.

There are currently two known subtypes, termed CB₁ and CB₂. The CB₁ receptor is expressed mainly in the brain (central nervous system, CNS), but also in the lungs, liver and kidneys. The CB₂ receptor is expressed mainly in the immune system and in hematopoietic cells. Mounting evidence suggests that there are novel cannabinoid receptors that is, non-CB₁ and non-CB₂, which are expressed in endothelial cells and in the CNS. In 2007, the binding of several cannabinoids to a G protein-coupled receptor (GPCR) in the brain was described.

The protein sequences of CB₁ and CB₂ receptors are about 44% similar. When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68%. In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. The affinity of an individual cannabinoid to each receptor determines the effect of that cannabinoid. Cannabinoids that bind more selectively to certain receptors are more desirable for medical usage.