ArticleThe Journal of biological chemistry2013
Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 184 citations in OpenAlex.
- Biological effects of leukotriene E4 on eosinophils.Prostaglandins, leukotrienes, and essential fatty acids · 2014Trial
- Autocrine CysLTOncogene · 2026Article
- Structural insights into ligand recognition and activation of the human oxoglutarate receptor OXGR1.Nature communications · 2026Article
- Structural analysis reveals that water molecules mediate self-activation of GPR99.Communications biology · 2026Article
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- A Narrative Review of Recent Developments in Aspirin Therapy After Desensitization in NSAIDs-Exacerbated Respiratory Disease.Journal of inflammation research · 2026Review
- Loss of OXGR1 function uncouples intrarenal RAS activation from pendrin and αENaC regulation and blunts angiotensin II-induced hypertension.Frontiers in pharmacology · 2026Article
- Molecular insights into ligand recognition and signaling of OXGR1.Nature communications · 2025Article
- Unraveling cysteinyl leukotrienes and their receptors in inflammation through the brain-gut-lung axis.Virulence · 2025Review
- Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens.Science (New York, N.Y.) · 2025Article
- Leukotrienes: Bridging the Inflammatory Gap in Asthma and Inflammatory Bowel Diseases (IBD).Comprehensive Physiology · 2025Review
- Cysteinyl Leukotrienes in Allergic Inflammation.Annual review of pathology · 2025Review
- OXGR1-Dependent (Pro)Renin Receptor Upregulation in Collecting Ducts of the Clipped Kidney Contributes to NaInternational journal of molecular sciences · 2024Article
- The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.The Journal of clinical investigation · 2023Article
- Short-term high fat feeding induces inflammatory responses of tuft cells and mucosal barrier cells in the murine stomach.Histology and histopathology · 2023Article
- Review
- Article
- Blockade of Platelet CysLT1R Receptor with Zafirlukast Counteracts Platelet Protumoral Action and Prevents Breast Cancer Metastasis to Bone and Lung.International journal of molecular sciences · 2022Article
- Leukotrienes vs. Montelukast-Activity, Metabolism, and Toxicity Hints for Repurposing.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Smooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation.Life metabolism · 2022Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The cysteinyl leukotrienes (cys-LTs), leukotriene C4 (LTC4), a conjugation product of glutathione and eicosatetraenoic acid, and its metabolites, LTD4 and LTE4, are lipid mediators of smooth muscle constriction and inflammation in asthma. LTD4 is the most potent ligand for the type 1 cys-LT receptor (CysLT1R), and LTC4 and LTD4 have similar lesser potency for CysLT2R, whereas LTE4 has little potency for either receptor. Cysltr1/Cysltr2(-/-) mice, lacking the two defined receptors, exhibited a comparable dose-dependent vascular leak to intradermal injection of LTC4 or LTD4 and an augmented response to LTE4 as compared with WT mice. As LTE4 retains a cysteine residue and might provide recognition via a dicarboxylic acid structure, we screened cDNAs within the P2Y nucleotide receptor family containing CysLTRs and dicarboxylic acid receptors with trans-activator reporter gene assays. GPR99, previously described as an oxoglutarate receptor (Oxgr1), showed both a functional and a binding response to LTE4 in these transfectants. We generated Gpr99(-/-) and Gpr99/Cysltr1/Cysltr2(-/-) mice for comparison with WT and Cysltr1/Cysltr2(-/-) mice. Strikingly, GPR99 deficiency in the Cysltr1/Cysltr2(-/-) mice virtually eliminated the vascular leak in response to the cys-LT ligands, indicating GPR99 as a potential CysLT3R active in the Cysltr1/Cysltr2(-/-) mice. Importantly, the Gpr99(-/-) mice showed a dose-dependent loss of LTE4-mediated vascular permeability, but not to LTC4 or LTD4, revealing a preference of GPR99 for LTE4 even when CysLT1R is present. As LTE4 is the predominant cys-LT species in inflamed tissues, GPR99 may provide a new therapeutic target.
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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.