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Review
. 2010 Jun;126(3):301-13.
doi: 10.1016/j.pharmthera.2010.02.004. Epub 2010 Mar 16.

Pharmacological characterization of GPR55, a putative cannabinoid receptor

Haleli Sharir  1 , Mary E Abood
Affiliations
Review

Pharmacological characterization of GPR55, a putative cannabinoid receptor

Haleli Sharir et al. Pharmacol Ther. 2010 Jun.

Abstract

GPR55 has recently attracted much attention as another member of the cannabinoid family, potentially explaining physiological effects that are non-CB1/CB2 mediated. However, the data gathered so far are conflicting with respect to its pharmacology. We review the primary literature to date on GPR55, describing its discovery, structure, pharmacology and potential physiological functions. The CB1 receptor antagonist/inverse agonist AM251 has been shown to be a GPR55 agonist in all reports in which it was evaluated, as has the lysophospholipid, lysophosphatidylinositol (LPI). Whether GPR55 responds to the endocannabinoid ligands anandamide and 2-arachidonylglycerol and the phytocannabinoids, delta-9-tetrahydrocannabidiol and cannabidiol, is cell type and tissue-dependent. GPR55 has been shown to utilize G(q), G(12), or G(13) for signal transduction; RhoA and phospholipase C are activated. Experiments with mice in which GPR55 has been inactivated reveal a role for this receptor in neuropathic and inflammatory pain as well as in bone physiology. Thus delineating the pharmacology of this receptor and the discovery of selective agonists and antagonists merits further study and could lead to new therapeutics.

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Figures

Figure 1
Figure 1
The structures of several compounds studied as GPR55 ligands. Lysophosphatidylinositol (LPI) and 2-arachidonyl-glycero-3-phosphoinositol (2AGPI) are lyosphospholipid agonists of GPR55. Anandamide and 2-arachidonylglycerol (2-AG) are endocannabinoids. THC is a phytocannabinoid and CP55,940 the prototypical non-classic cannabinoid agonist. WIN55,212-2 is the prototypical aminoalkylindole compound. SR141716A, AM251 and AM281 are pyrazole CB1 receptor antagonists/inverse agonists.
Figure 2
Figure 2
Helix net representation of human GPR55. The residues shaded in black represent highly conserved residues in rhodopsin, the prototypical Class A GPCR.
Figure 3
Figure 3
A summary of the signaling pathways initiated by GPR55.
See this image and copyright information in PMC

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