ArticleThe Journal of clinical investigation2010
Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Blunted Niacin Skin Flushing Response in Schizophrenia: A Meta-analysis.Schizophrenia bulletin · 2026Pooled it
- Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy.Pharmacogenetics and genomics · 2017Trial
- Similar maximum systemic but not local cyclooxygenase-2 inhibition by 50 mg lumiracoxib and 90 mg etoricoxib: a randomized controlled trial in healthy subjects.Pharmaceutical research · 2014Trial
- HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment.European heart journal · 2013Trial
- Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.The Journal of clinical investigation · 2012 · on this mapTrial
- Trial
- Clinical application of niacin-induced skin flush response in adolescents with psychiatric disorders and its correlation with clinical blood test indicators.BMC psychiatry · 2026Article
- Blunted niacin skin flushing response with subtype-specific clinical associations in adolescent bipolar disorder.BMC psychiatry · 2026Article
- A transdiagnostic niacin flushing biomarker with disorder-specific multivariate relationships in adolescent unipolar and bipolar depression.BMC psychiatry · 2026Article
- Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and prospects.Frontiers in medicine · 2026Review
- Microbiota shape the colon epithelium controlling inter-crypt absorptive goblet cells via butyrate-GP R109A signalling.Gut microbes · 2025Article
- Structures of G-protein coupled receptor HCAR3 in complex with selective agonists reveal the basis for ligand recognition and selectivity.PLoS biology · 2025Article
- Fumarate Signaling in Cardiovascular Disease: Therapeutic Potential and Pathologic Pitfalls of DMF/MMF and FH1 Deficiency.Journal of cardiovascular translational research · 2025Review
- High Concentrations of Circulating 2PY and 4PY-Potential Risk Factor of Cardiovascular Disease in Patients with Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Article
- Structures of G-protein coupled receptor HCAR1 in complex with Gi1 protein reveal the mechanistic basis for ligand recognition and agonist selectivity.PLoS biology · 2025Article
- Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode.Nature communications · 2024Review
- GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular Respiration.The Journal of investigative dermatology · 2024Article
- The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.Cureus · 2024Review
- Supplementation of Nicotinic Acid and Its Derivatives Up-Regulates Cellular NADLife (Basel, Switzerland) · 2024Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of monomethyl fumarate. Here we analyzed the mechanisms underlying GPR109A-mediated flushing and show that both Langerhans cells and keratinocytes express GPR109A in mice. Using cell ablation approaches and transgenic cell type-specific GPR109A expression in Gpr109a-/- mice, we have provided evidence that the early phase of flushing depends on GPR109A expressed on Langerhans cells, whereas the late phase is mediated by GPR109A expressed on keratinocytes. Interestingly, the first phase of flushing was blocked by a selective cyclooxygenase-1 (COX-1) inhibitor, and the late phase was sensitive to a selective COX-2 inhibitor. Both monomethyl fumarate and nicotinic acid induced PGE2 formation in isolated keratinocytes through activation of GPR109A and COX-2. Thus, the early and late phases of the GPR109A-mediated cutaneous flushing reaction involve different epidermal cell types and prostanoid-forming enzymes. These data will help to guide new efficient approaches to mitigate nicotinic acid-induced flushing and may help to exploit the potential antipsoriatic effects of GPR109A agonists in the skin.
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Registered trials
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 Socratic graph.