GPR55

G protein-coupled receptor 55 also known as GPR55 is a G protein-coupled receptor that in humans is encoded by the GPR55 gene.^[5]

GPR55, along with

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.[18]^[19][20][21] However this is complicated by the fact that another possible CB₃ receptor has been discovered in the hippocampus, although its gene has not yet been cloned,^[22] 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.^[23]

Ligands

Agonists

Ligands found to bind to GPR55 as agonists include:

• Lysophosphatidylinositol
• 2-Arachidonoyl lysophosphatidylinositol
• Abnormal cannabidiol (Abn-CBD)
• AM-251
  (also CB₁ antagonist)
• CP 55,940
• GSK-319,197
• GSK-494,581 - also glycine transporter 1 inhibitor ^[24]
• GSK-522,373
• O-1602
• Δ⁹-Tetrahydrocannabinol^[12]
• Tetrahydrocannabivarin (THCV)
• 2-Arachidonoylglycerol (2-AG)^[12]
• Noladin ether
• Oleoylethanolamide
• Palmitoylethanolamide
• ML-184, ML-185 and ML-186 ^[25]

Antagonists

• CID-16020046
  - inverse agonist at GPR55
• O-1918
• ML-191, ML-192 and ML-193^[25]
• PSB-SB-487 and PSB-SB-1203 ^[26]
• Cannabidiol^[12]

Physiological function

The physiological role of GPR55 is unclear. Mice with a target deletion of the GPR55 gene show no specific phenotype.^[10] GPR55 is widely expressed in the brain, especially in the cerebellum. It is expressed in the jejunum and ileum but apparently not more generally in the periphery.^[12] Osteoblasts and osteoclasts express GPR55 and this has been shown to regulate bone cell function.^[27]

References