GPR55

G protein-coupled receptor 55, also known as GPR55, is a human gene which encodes the protein for the GPR-55 receptor.

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

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

Pharmacology
GPR55 is activated by the plant cannabinoids Δ9-THC and cannabidiol, and the endocannabinoids anandamide, 2-AG, noladin ether in the low nanomolar range. The synthetic cannabinoid CP-55940 is also able to activate the receptor while the structurally unrelated cannabinoid mimic WIN 55,212-2 fails to activate the receptor.

Physiological function
The physiological role of GPR55 is unclear. Mice with a target deletion of the GPR55 gene show no specific phenotype. GPR55 is widely expressed in the brain, especially in the cerebellum. Except for the jejunum and ileum it is not expressed in the periphery.