EndoCANNABINOIDS: Actions at Non-CB1/CB2 Cannabinoid Receptors: 24 (The Receptors)

Cannabinoid-Related Oligomers Numerous studies have shown that GPCRs, cannabinoid receptors among them, can exist and function as dimers or complexes of higher order. Author Disclosure Statement No competing financial interests exist. Targeting the endocannabinoid system with cannabinoid receptor agonists: Philos Trans R Soc B ; Molecular targets of the phytocannabinoids: Kinghorn AD, editor; , Gibbons S, editor.

Unraveling the Complex Chemistry and Pharmacology of Cannabis sativa. Springer International Publishing, ; Vol. International union of basic and clinical pharmacology. Cannabinoid receptors and their ligands: Pharmacol Rev ; The enigmatic pharmacology of GPR Trends Pharmacol Sci ; Pharmacology, signaling and physiological relevance of the G protein-coupled receptor Pharmacology of G Protein Coupled Receptors.

Advances in Pharmacology, Volume 62 , Elsevier Inc. GPR55 is extensively expressed in human brain. Mol Brain Res ; The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol ; GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. GPR55 ligands promote receptor coupling to multiple signalling pathways.

Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. Inflammatory and neuropathic nociception is preserved in GPR55 knockout mice. Sci Rep ; 7: The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. J Mol Endocrinol ; R—R [ PubMed ].

GPR55 and the regulation of glucose homeostasis. Int J Biochem Cell Biol ; The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces calcium release in rat mesenteric artery endothelial cells. Vascul Pharmacol ; The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo.

GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination. PLoS One ; 8: Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun ; J Biochem ; Lysophospholipid receptor nomenclature review: Curr Med Chem ; Nevalainen T, Irving AJ.

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GPR55, a Lysophosphatidylinositol receptor with cannabinoid sensitivity? Curr Top Med Chem ; 1: Sharir H, Abood ME. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther ; Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay.

J Biol Chem ; Morales P, Jagerovic N. Advances towards the discovery of GPR55 ligands. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci ; Cloning and chromosomal localization of a gene GPR18 encoding a novel seven transmembrane receptor highly expressed in spleen and testis. Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR Activation of GPR18 by cannabinoid compounds: N-arachidonoyl glycine induces macrophage apoptosis via GPR Evidence for a GPR18 role in diurnal regulation of intraocular pressure.

Invest Ophthalmol Vis Sci ; Pigment Cell Melanoma Res ; G protein coupled receptor Mol Nutr Food Res ; N-arachidonyl glycine does not activate G protein—coupled receptor 18 signaling via canonical pathways. Mol Pharmacol ; Identification of resolvin D2 receptor mediating resolution of infections and organ protection.

J Exp Med ; Identification of crucial amino acid residues involved in agonist signaling at the GPR55 receptor. Fredriksson R, Schio HB. The repertoire of G-protein—coupled receptors in fully. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Methods for the development of in silico GPCR models. Cannabinoids and Their Receptors.

Methods in Enzymology, Volume , Elsevier Inc. Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem J ; Molecular cloning and chromosomal localization of human genes encoding three closely related G protein-coupled receptors. Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors.

Cell Signal ; Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development. J Neurosci ; Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. Sci Transl Med ; 7: Nelson CD, Sheng M. Nat Med ; The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development.

PLoS One ; 4: Developmental expression of GPR3 in rodent cerebellar granule neurons is associated with cell survival and protects neurons from various apoptotic stimuli. Neurobiol Dis ; GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception. The orphan receptor GPR3 modulates the early phases of cocaine reinforcement.

GPR3 receptor, a novel actor in the emotional-like responses. Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6. Nat Neurosci ; G-protein coupled receptor 6 deficiency alters striatal dopamine and cAMP concentrations and reduces dyskinesia in a mouse model of Parkinson's disease.

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Exp Neurol ; Oeckl P, Ferger B. Dev Biol ; The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice. Involvement of GPR12 in the regulation of cell proliferation and survival. Mol Cell Biochem ; International Union of Basic and Clinical Pharmacology. G protein-coupled receptor list: Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J Biomol Screen ; Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus.

Novel, not adenylyl cyclase-coupled cannabinoid binding site in cerebellum of mice. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain.

Cannabinoid receptors and endocannabinoids: Evidence for new players

Alkylindole-sensitive receptors modulate microglial cell migration and proliferation. Novel indole-based compounds that differentiate alkylindole-sensitive receptors from cannabinoid receptors and microtubules: Pharmacol Res ; Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS One ; 5: Mol Cancer Ther ; Basic pharmacological and structural evidence for class A G-protein-coupled receptor heteromerization. Front Pharmacol ; 7: Revealing G-protein-coupled receptor oligomerization at the single-molecule level through a nanoscopic lens: FEBS J ; G protein-coupled receptor multimers: Cognitive impairment induced by Delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors.

PLoS Biol ; EMBO J ; Dimerization with cannabinoid receptors allosterically modulates delta opioid receptor activity during neuropathic pain. PLoS One ; 7: Revolution in GPCR signalling: J Pharmacol Sci ; CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum.

Recent experimental and computational results discussed in this review have suggested that this may be true. However, more research needs to be done in this area.

Finally, our current thinking about the location of key components of the endocannabinoid system synthesizing enzymes, receptor protein and degrading enzymes , as described in this review still involves endocannabinoids crossing the synaptic cleft. Given endocannabinoid high lipophilicity, the deduction of how such a movement across the cleft occurs will be a very great contribution to the field.

National Center for Biotechnology Information , U. Author manuscript; available in PMC Aug 4. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Curr Med Chem. See other articles in PMC that cite the published article. Open in a separate window. AEA Acyl Chain SAR Endocannabinoid SAR indicates that the CBI receptor recognizes ethanolamides whose fatty acid acyl chains have 20 or 22 carbons, with at least three homoallylic double bonds and saturation in at least the last five carbons of the acyl chain [ ].

Molecular Dynamics Simulations in Lipid Multi-nanosecond molecular dynamics simulations of AEA in a 1,2-dioleoyl- sn -glycerophosphocholine DOPC phospholipid bilayer have suggested that the AEA polar headgroup resides at the lipid-water interface, specifically in the polar phospholipid headgroup region, whereas the AEA nonpolar acyl chain extends into the hydrocarbon core of the membrane. Mutation Studies of the CB1 and CB2 Receptors Mutation and chimera studies are excellent ways to gather information on ligand binding sites. Structure of a cannabinoid receptor and functional expression of the cloned cDNA.

1. Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown.
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A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Inverse agonist properties of N- piperidin-l-yl 4-chloro-phenyl -l- 2,4-dichlorophenyl methyl-lH-pyrazolecarboxa-mide HC1 SRA and l- 2-chlorophenyl cyano 4-methoxyphenyl -lH-pyrazolecarboxyl ic acid phenylamide CP for the CB 1 cannabinoid receptor. Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine. Synthesis and characterization of a peripherally restricted CB1 cannabinoid antagonist, URB, that reduces feeding and body-weight gain in mice.

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Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB 2 receptor. Relative involvement of cannabinoid CB 1 and CB 2 receptors in the Delta 9 -tetrahydrocannabinol-induced inhibition of natural killer activity. Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoyl-glycerol. Franklin A, Stella N. Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors.

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In vitro and in vivo pharmacological characterization of JTE, a novel selective ligand for cannabinoid CB2 receptor. Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: Triaryl bis-sulfones as cannabinoid-2 receptor ligands: GPR55 is extensively expressed in human brain.

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The orphan receptor GPR55 is a novel cannabinoid receptor. The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Identification of GPR55 as a lysophosphatidylinositol receptor.

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Cannabinoid receptors and endocannabinoids: Evidence for new players

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Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown

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