ArticleMolecular pharmacology2013
N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
- Structure Prediction, Evaluation, and Validation of GPR18 Lipid Receptor Using Free Programs.International journal of molecular sciences · 2022Article
- Endocannabinoid signaling pathways: beyond CB1R and CB2R.Journal of cell communication and signaling · 2021Review
- Phytocannabinoids Biosynthesis in Angiosperms, Fungi, and Liverworts and Their Versatile Role.Plants (Basel, Switzerland) · 2021Review
- Biosynthesis of Nature-Inspired Unnatural Cannabinoids.Molecules (Basel, Switzerland) · 2021Review
- Effects of GPR18 Ligands on Body Weight and Metabolic Parameters in a Female Rat Model of Excessive Eating.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Therapeutic Exploitation of GPR18: Beyond the Cannabinoids?Journal of medicinal chemistry · 2020Review
- Endocannabinoid metabolism and transport as targets to regulate intraocular pressure.Experimental eye research · 2020Article
- Discovery of Tricyclic Xanthines as Agonists of the Cannabinoid-Activated Orphan G-Protein-Coupled Receptor GPR18.ACS medicinal chemistry letters · 2020Article
- Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18.Biomolecules · 2020Article
- Inhibition of store-operated calcium channels by N-arachidonoyl glycine (NAGly): no evidence for the involvement of lipid-sensing G protein coupled receptors.Scientific reports · 2020Article
- Review
- Article
- Towards A Molecular Understanding of The Cannabinoid Related Orphan Receptor GPR18: A Focus on Its Constitutive Activity.International journal of molecular sciences · 2019Article
- Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures.International journal of molecular sciences · 2019Article
- Modulation of the Endocannabinoid System as a Potential Anticancer Strategy.Frontiers in pharmacology · 2019Review
- Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues.Antioxidants (Basel, Switzerland) · 2018Review
- The quest for endothelial atypical cannabinoid receptor: BKVascular pharmacology · 2018Article
- Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55.Frontiers in pharmacology · 2018Review
- N-arachidonoyl glycine, another endogenous agonist of GPR55.Biochemical and biophysical research communications · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the Gα(i/o) protein-coupled receptor 18 (GPR18). However, a high-throughput β-arrestin-based screen failed to detect activation of GPR18 by NAGly (Yin et al., 2009; JBC, 18:12328). To address this inconsistency, this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors. GPR18 was heterologously expressed in rat sympathetic neurons, and the modulation of N-type (Ca(v)2.2) calcium channels was examined. Proper expression and trafficking of receptor were confirmed by the "rim-like" fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin-tagged GPR18-expressing cells. Application of NAGly on GPR18-expressing neurons did not inhibit calcium currents but instead potentiated currents in a voltage-dependent manner, similar to what has previously been reported (Guo et al., 2008; J Neurophysiol, 100:1147). Other proposed agonists of GPR18, including anandamide and abnormal cannabidiol, also failed to induce inhibition of calcium currents. Mutants of GPR18, designed to constitutively activate receptors, did not tonically inhibit calcium currents, indicating a lack of GPR18 activation or coupling to endogenous G proteins. Other downstream effectors of Gα(i/o)-coupled receptors, G protein-coupled inwardly rectifying potassium channels and adenylate cyclase, were not modulated by GPR18 signaling. Furthermore, GPR18 did not couple to other G proteins tested: Gα(s), Gα(z), and Gα(15). These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.