ArticleCirculation research2017
20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (G
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Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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114citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
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Who cites it
114 citing papers in PubMed, 178 citations in OpenAlex.
- SGLT2 inhibitor ameliorates hypertension by regulating the CYP4A/20-HETE pathway in the kidney.Bioscience reports · 2026Article
- G protein-coupled receptor 75 mediates depression-like behaviors and HPA axis hyperactivity through an excitatory arcuate-paraventricular nucleus circuit.Acta pharmacologica Sinica · 2026Article
- GPR75 mediates hyperuricemia-induced endothelial inflammatory injury via a HOTAIR/miR-141-3p regulatory network.Molecular biology reports · 2026Article
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Lgr6Genes & diseases · 2026Review
- The 20-HETE/GPR75 Axis Drives NLRP1 Inflammasome Activation via p53 in Bronchopulmonary Dysplasia.Advanced biology · 2026Article
- Blood multiomics reveal a dysregulated lipid mediator-mitochondrial network associated with the outcome of advanced cirrhosis.Nature communications · 2026Article
- Maternal obesity induces macrophage to myofibroblast transition in kidneys of male offspring through a pathway driven by 20-hydroxyeicosatetraenoic acid.Nature communications · 2026Article
- Cryo-EM structures of GPR75 reveal an occluded orthosteric pocket challenging conventional drug discovery paradigms for an anti-obesity target.Acta pharmacologica Sinica · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- GPR75 in glutamatergic neurons regulates body weight.Cell reports · 2026Article
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Anatomical and Neuronal Distribution of the G-Coupled Protein Receptor 75 mRNA in the Mouse Central Nervous System.The European journal of neuroscience · 2026Article
- Sex-dependent role of 20-HETE synthesis in outcome from ischemic stroke in rats.Physiological reports · 2026Article
- Neuronal GPR75 deficiency protects against diet-induced obesity in a humanized mouse model.Science advances · 2026Article
- G Protein-Coupled Receptors in Cerebrovascular Diseases: Signaling Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Orphan GPCRs in diabetes mellitus: metabolic control, inflammation, and drug development.Frontiers in endocrinology · 2026Review
- On the interface of fatty acid metabolism: A crosstalk between fatty acid ω-hydroxylase CYP4F11 and fatty acid desaturase 2 in non-small cell lung cancer.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis.Nature communications · 2025Article
- GPR75 signaling is dispensable for reproduction but contributes to feeding and body growth in rats on normal chow and is involved in high-fat diet-induced hyperphagia, obesity, and hyperglycemia development.Endocrine journal · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Victor GarciaFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Ankit GilaniFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Brian ShkolnikFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Varunkumar PandeyFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Frank Fan ZhangFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Rambabu DakarapuFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Shyam K GandhamFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
N Rami ReddyFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Joan P GravesFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Artiom GruzdevFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Darryl C ZeldinFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Jorge H CapdevilaFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
John R FalckFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.).
Michal Laniado SchwartzmanFrom the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.). Michal_schwartzman@nymc.edu.
National Institutes of Health · USNational Institute of Environmental Health Sciences · USThe University of Texas Southwestern Medical Center · US
Funding
Vasoregulatory Function of CYP2E1-Derived EicosanoidsP01HL034300 · NHLBI · NEW YORK MEDICAL COLLEGE · PI JIANG, HOULI · 1985 to 2015
$33.4MTRANSPORT EFFECTS OF ARACHIDONATE METABOLITES IN PERFUSED TUBULEP01DK038226 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROWN, NANCY J. · 1986 to 2015
$22.1M NIEHS Knock Out Mouse Core (KOMC) Annual ReportZICES102425 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI RAY, MANAS · 2010 to 2025
$20.1MCharacterization And Functional Significance Of P450 Arachidonate EpoxygenasesZIAES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 2009 to 2025
$18.6MP450 Arachidonate EpoxygenasesZ01ES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 1995 to 2008
$2.2MIntramural NIH HHS Z01 ES025034NHLBI NIH HHS P01 HL034300NIDDK NIH HHS P01 DK038226
Abstract
rationale20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases.
objectiveTo date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists. The present study was undertaken to identify a receptor to which 20-HETE binds and through which it activates a signaling cascade that culminates in many of the functional outcomes attributed to 20-HETE in vitro and in vivo. METHODS AND
resultsUsing crosslinking analogs, click chemistry, binding assays, and functional assays, we identified G-protein receptor 75 (GPR75), currently an orphan G-protein-coupled receptor (GPCR), as a specific target of 20-HETE. In cultured human endothelial cells, 20-HETE binding to GPR75 stimulated Gα
conclusionsThis is the first report to identify a GPCR target for an eicosanoid of this class. The discovery of 20-HETE-GPR75 pairing presented here provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases.
Indexed as
AnimalsCells, CulturedEndothelium, VascularHumansHydroxyeicosatetraenoic AcidsHypertensionMaleMiceMice, TransgenicProtein BindingRatsReceptors, G-Protein-CoupledSignal TransductionVascular Remodeling20-hydroxy-5,8,11,14-eicosatetraenoic acidGPR75 protein, humanHydroxyeicosatetraenoic AcidsReceptors, G-Protein-Coupledcardiovascular diseasescytochrome P-450 enzyme systemhypertensionreceptor, epidermal growth factorvascular remodeling
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