GPR55

G protein-coupled receptor 55 also known as GPR55 is a is_associated_with::G protein-coupled receptor that in humans is encoded by the GPR55 is_associated_with::gene.

GPR55, along with is_associated_with::GPR119 and is_associated_with::GPR18, have been implicated as novel is_associated_with::cannabinoid receptors.

History
GPR55 was identified and cloned for the first time in 1999. Later it was identified by an is_associated_with::in silico screen as a putative cannabinoid receptor because of a similar amino acid sequence in the binding region. Research groups from is_associated_with::Glaxo Smith Kline and is_associated_with::Astra Zeneca characterized the receptor extensively because it was hoped to be responsible for the blood pressure lowering properties of cannabinoids. GPR55 is indeed activated by endogenous, plant and synthetic is_associated_with::cannabinoids but GPR-55 knockout mice generated by a research group from is_associated_with::Glaxo Smith Kline showed no altered blood pressure regulation after administration of the is_associated_with::cannabidiol-derivative is_associated_with::abnormal cannabidiol.

Signal cascade
GPR55 is coupled to the is_associated_with::G-protein G13 and activation of the receptor leads to stimulation of is_associated_with::rhoA, is_associated_with::cdc42 and is_associated_with::rac1.

Pharmacology
GPR55 is activated by the plant cannabinoids Δ9-THC and cannabidiol, and the is_associated_with::endocannabinoids is_associated_with::anandamide, is_associated_with::2-AG, is_associated_with::noladin ether in the low nanomolar range. The synthetic cannabinoid is_associated_with::CP-55940 is also able to activate the receptor while the structurally unrelated cannabinoid mimic is_associated_with::WIN 55,212-2 fails to activate the receptor. Recent research suggests that lysophosphatidylinositol and its 2-arachidonoyl derivative may be the endogenous ligands for GPR55,  and the receptor appears likely to be a possible target for treatment of inflammation and pain as with the other cannabinoid receptors.

This profile as a distinct non-CB1/CB2 receptor which responds to a variety of both endogenous and exogenous cannabinoid ligands, has led some groups to suggest GPR55 should be categorised as the CB3 receptor, and this re-classification may follow in time. However this is complicated by the fact that another possible CB3 receptor has been discovered in the is_associated_with::hippocampus, although its gene has not yet been cloned, suggesting that there may be at least four cannabinoid receptors which will eventually be characterised. Evidence accumulated during the last few years suggests that GPR55 plays a relevant role in cancer and opens the possibility of considering this orphan receptor as a new therapeutic target and potential biomarker in oncology.

Ligands
Ligands found to bind to GPR55 as agonists include:
 * Agonists
 * is_associated_with::Lysophosphatidylinositol
 * is_associated_with::Abnormal cannabidiol (Abn-CBD)
 * AM-251 (also CB1 antagonist)
 * is_associated_with::CP 55,940
 * GSK-319,197
 * GSK-494,581 - also glycine transporter 1 inhibitor
 * GSK-522,373
 * is_associated_with::O-1602
 * Δ9-Tetrahydrocannabinol
 * is_associated_with::2-Arachidonoylglycerol (2-AG)
 * is_associated_with::Noladin ether
 * is_associated_with::Oleoylethanolamide
 * is_associated_with::Palmitoylethanolamide
 * ML-184, ML-185 and ML-186


 * Antagonists
 * is_associated_with::CID-16020046 - inverse agonist at GPR55
 * is_associated_with::O-1918
 * ML-191, ML-192 and ML-193
 * is_associated_with::PSB-SB-487 and PSB-SB-1203
 * is_associated_with::Cannabidiol

Physiological function
The physiological role of GPR55 is unclear. Mice with a target deletion of the GPR55 gene show no specific is_associated_with::phenotype. GPR55 is widely expressed in the brain, especially in the is_associated_with::cerebellum. It is expressed in the is_associated_with::jejunum and is_associated_with::ileum but apparently not more generally in the periphery. is_associated_with::Osteoblasts and is_associated_with::osteoclasts express GPR55 and this has been shown to regulate bone cell function.