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This Article Full Text Full Text (PDF) All Versions of this Article: jpet.108.141333v1 327/3/665    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Papaliodis, D. Articles by Theoharides, T. C. Search for Related Content PubMed PubMed Citation Articles by Papaliodis, D. Articles by Theoharides, T. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NICOTINIC ACID

CARDIOVASCULAR

Niacin-induced "Flush" Involves Release of Prostaglandin D₂ from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Department of Pharmacology and Experimental Therapeutics, Molecular Immunopharmacology and Drug Discovery Laboratory (D.P., W.B., D.K., M.M., T.C.T.) and Departments of Obstetrics and Gynecology (A.W., M.H.), Internal Medicine (T.C.T.), and Biochemistry (T.C.T.), Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts

Niacin lowers serum cholesterol, low-density lipoprotein, and triglycerides, and it raises high-density lipoprotein. However, most patients experience cutaneous warmth and vasodilation (flush). Acetylsalicylic acid (ASA) can reduce this flush, presumably by decreasing prostaglandin D₂ (PGD₂) release from macrophages. Here, we show that methylnicotinate induces significant PGD₂ release from human mast cells and serotonin from human platelets. Intradermal injection of methylnicotinate induces rat skin vasodilation and vascular permeability. Niacin increases plasma PGD₂ and serotonin in a rat model of flush. The phenothiazine prochlorperazine, the H₁, serotonin receptor antagonist cyproheptadine, and the specific serotonin receptor-2A antagonist ketanserin inhibit niacin-induced temperature increase by 90% (n = 5, p < 0.05), 90 and 50% (n = 3, p < 0.05), and 85% (n = 6, p = 0.0008), respectively, in this animal model. These results indicate that niacin-induced flush involves both PGD₂ and serotonin, suggesting that drugs other than ASA are required to effectively inhibit niacin-induced flush.

Address correspondence to: Dr. Theoharis Constantin Theoharides, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111. E-mail: theoharis.theoharides{at}tufts.edu