GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors.
Source
Center for Substance Abuse Research and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA, USA.
Abstract
This review presents a summary of what is known about the G-protein coupled receptors GPR35 and GPR55 and their potential characterization as lysophospholipid or cannabinoid receptors, respectively. Both GPR35 and GPR55 have been implicated as important targets in pain and cancer, and additional diseases as well. While kynurenic acid was suggested to be an endogenous ligand for GPR35, so was 2-arachidonoyl lysophosphatidic acid (LPA). Similarly, GPR55 has been suggested to be a cannabinoid receptor, but is quite clearly also a receptor for lysophosphatidylinositol. Interestingly, 2-arachidonyl glycerol (2-AG), an endogenous ligand forcannabinoid receptors, can be metabolized to 2-arachidonoyl LPA through the action of a monoacylglycerol kinase; the reverse reaction has also been demonstrated. Thus, it appears that mutual interconversion is possible between 2-arachidonoyl LPA and 2-AG within a cell, though the direction of the reaction may be site-dependent. The GPR55 natural ligand, 2-arachidonoyl LPI, can be degraded either to 2-AG by phospholipase C or to 2-arachidonoyl LPA by phospholipase D. Thus, GPR35, GPR55 and CB receptors are linked together through their natural ligand conversions. Additional agonists and antagonists have been identified for both GPR35 and GPR55, which will facilitate the future study of these receptors with respect to their physiological function. Potential therapeutic targets include pain, cancer, metabolic diseases and drug addiction.
Copyright © 2012 Elsevier Inc. All rights reserved.
Copyright © 2012 Elsevier Inc. All rights reserved.
- PMID:
22820167
[PubMed – indexed for MEDLINE]
Publication Types, MeSH Terms, Substances, Grant Support
Publication Types
MeSH Terms
- Animals
- Cannabinoids/pharmacology
- Cannabinoids/therapeutic use
- Gene Expression
- Humans
- Ligands
- Receptors, Cannabinoid/drug effects
- Receptors, Cannabinoid/genetics
- Receptors, Cannabinoid/physiology*
- Receptors, G-Protein-Coupled/biosynthesis
- Receptors, G-Protein-Coupled/drug effects
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/physiology*
- Receptors, Lysophospholipid/drug effects
- Receptors, Lysophospholipid/genetics
- Receptors, Lysophospholipid/physiology*
Substances
- Cannabinoids
- GPR35 protein, human
- GPR55 protein, human
- Ligands
- Receptors, Cannabinoid
- Receptors, G-Protein-Coupled
- Receptors, Lysophospholipid
Grant Support
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Full Text Sources
Graphical abstract
Illustration of metabolic relationships between 2-acyl LPA, 2-acyl LPI and 2-AG and their cognate receptors. The lipid ligands can interconvert and interact with GPR35, GPR55 and cannabinoid receptors.
Keywords
- G-protein coupled receptor;
- Cannabinoid;
- GPR35;
- GPR55;
- Lysophospholipid
Figures and tables from this article:
- Fig. 1. Structures of ligands and related compounds. The three endogenous ligands, 2-arachidonyl LPA (2-acyl LPA), 2-arachidonyl LPI (2-acyl LPA) and 2-arachidonyl glycerol (2-AG) for GPR35, GPR55 and cannabinoid receptors are structurally related. Kynurenic acid is another GPR35 endogenous agonist. Kynurenine and tryptophan are two compounds related to kynurenic acid.
- Fig. 2. Illustration of metabolic relationships between 2-acyl LPA, 2-acyl LPI and 2-AG and their cognate receptors. The lipid ligands can interconvert and interact with GPR35, GPR55 and cannabinoid receptors.
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Copyright © 2012 Elsevier Inc. All rights reserved.
