ArticleThe Journal of pharmacology and experimental therapeutics2014
The novel endocannabinoid receptor GPR18 is expressed in the rostral ventrolateral medulla and exerts tonic restraining influence on blood pressure.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
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- GPCRs: emerging targets for novel T cell immune checkpoint therapy.Cancer immunology, immunotherapy : CII · 2024Review
- Hexahydrocannabinol (HHC) and ΔScientific reports · 2024Article
- A review of the direct targets of the cannabinoids cannabidiol, Δ9-tetrahydrocannabinol, N-arachidonoylethanolamine and 2-arachidonoylglycerol.AIMS neuroscience · 2024Review
- Pharmacognosy and Effects of Cannabinoids in the Vascular System.ACS pharmacology & translational science · 2022Review
- Acute and long-term effects of cannabinoids on hypertension and kidney injury.Scientific reports · 2022Article
- Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?Cells · 2022Review
- GPR18-Mediated Relaxation of Human Isolated Pulmonary Arteries.International journal of molecular sciences · 2022Article
- Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy.Nature communications · 2021Article
- Endocannabinoid signaling pathways: beyond CB1R and CB2R.Journal of cell communication and signaling · 2021Review
- The GPR18 Agonist PSB-KD-107 Exerts Endothelium-Dependent Vasorelaxant Effects.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Therapeutic Exploitation of GPR18: Beyond the Cannabinoids?Journal of medicinal chemistry · 2020Review
- The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease.International journal of molecular sciences · 2020Review
- Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure.Oxidative medicine and cellular longevity · 2020Review
- Cannabinoids and the expanded endocannabinoid system in neurological disorders.Nature reviews. Neurology · 2020Review
- Antioxidative and Anti-Inflammatory Properties of Cannabidiol.Antioxidants (Basel, Switzerland) · 2019Review
- Activation of the cannabinoid receptor 2 increases renal perfusion.Physiological genomics · 2019Article
- Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding.Current neuropharmacology · 2019Review
- Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues.Antioxidants (Basel, Switzerland) · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Systemic administration of the G-protein-coupled receptor 18 (GPR18) agonist abnormal cannabidiol (Abn CBD) lowers blood pressure (BP). Whether GPR18 is expressed in the central nervous system (CNS) and plays a role in BP control is not known despite the abundance of the GPR18 ligand N-arachidonoyl glycine (NAGly) in the CNS. Therefore, we first determined whether GPR18 is expressed in the presympathetic tyrosine hydroxylase (TH) immunoreactive (ir) neurons of the brainstem cardiovascular regulatory nuclei. Second, we investigated the impact of GPR18 activation and blockade on BP and heart rate (HR) and neurochemical modulators of sympathetic activity and BP. Immunofluorescence findings revealed GPR18 expression in TH-ir neurons in the rostral ventrolateral medulla (RVLM). Intra-RVLM GPR18 activation (Abn CBD) and blockade (O-1918, 1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-,cyclohexen-1-yl]benzene) elicited dose-dependent reductions and elevations in BP, respectively, along with respective increases and decreases in HR in conscious male Sprague-Dawley rats. RVLM GPR18 activation increased neuronal adiponectin (ADN) and NO and reduced reactive oxygen species (ROS) levels, and GPR18 blockade reduced neuronal ADN and increased oxidative stress (i.e., ROS) in the RVLM. Finally, we hypothesized that the negligible hypotensive effect caused by the endogenous GPR18 ligand NAGly could be due to concurrent activation of CB(1)R in the RVLM. Our findings support this hypothesis because NAGly-evoked hypotension was doubled after RVLM CB(1)R blockade (SR141716, rimonabant). These findings are the first to demonstrate GPR18 expression in the RVLM and to suggest a sympathoinhibitory role for this receptor. The findings yield new insight into the role of a novel cannabinoid receptor (GPR18) in central BP control.
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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.