''N''-Arachidonyl glycine receptor (NAGly receptor), also known as G protein-coupled receptor 18 (GPR18), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''GPR18''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Along with the other previously

orphan receptor In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred ...

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. GPR55, along with GPR119 and GPR18, have been implicated as novel cannabinoid receptors. History GPR55 was ide ...

and

GPR119 G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the ''GPR119'' gene. GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors. Pharmacology GPR ...

, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cann ...

s. It has been found to be involved in the regulation of

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

. Research supports the hypothesis that GPR18 is the

abnormal cannabidiol Abnormal cannabidiol (Abn-CBD) is a synthetic regioisomer of cannabidiol, which unlike most other cannabinoids produces vasodilator effects, lowers blood pressure, and induces cell migration, cell proliferation and mitogen-activated protein kinas ...

receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

, initiates directed

microglia Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

in the CNS through activation of GPR18, though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons. Resolvin D2 (RvD2), a member of the

specialized proresolving mediators Specialization or Specialized may refer to: Academia * Academic specialization, may be a course of study or major at an academic institution or may refer to the field in which a specialist practices * Specialty (medicine), a branch of medical ...

(SPM) class of

polyunsaturated fatty acid In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...

metabolites, is an activating ligand for GPR18; RvD2 and its activation of GPR18 contribute to the resolution of inflammatory responses as well as inflammation-based and other diseases in animal models and are proposed to do so in humans. Furthermore, RvD2 is a metabolite of the

omega-3 fatty acid Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega−3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(''n''−3). It can be synthesized from alpha-linolenic acid or ...

(DHA); the metabolism of DHA to RvD2 and RvD2's activation of GPR18 is proposed to one among many other mechanisms for the anti-inflammatory and other beneficial effects attributed to omega-3 fatty acid-rich diets

Ligands

;Agonists Ligands found to bind to GPR18 as agonists include: * ''N''-Arachidonoylglycine (NAGly) *

Abnormal cannabidiol Abnormal cannabidiol (Abn-CBD) is a synthetic regioisomer of cannabidiol, which unlike most other cannabinoids produces vasodilator effects, lowers blood pressure, and induces cell migration, cell proliferation and mitogen-activated protein kinas ...

(Abn-CBD) * AM-251 - partial agonist *

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...

- partial agonist * CBG-DMH * O-1602 * Δ⁹-Tetrahydrocannabinol (Δ⁹-THC) - THC is actually a more potent agonist at GPR18 than at CB₁ or CB₂, with Ki of 0.96nM at GPR18, 8.1nM at GPR55, 25.1nM at CB₁ and 35.2nM at CB₂. *

Anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

(''N''-arachidonoyl ethanolamine, AEA) * Arachidonylcyclopropylamide (ACPA) * Resolvin D2 (RvD2) * PSB-KD107 * PSB-KK1415 ;Antagonists * Amauromine * O-1918 * PSB-CB5

Ligands

References

Further reading