TY - JOUR T1 - Niacin-induced “Flush” Involves Release of Prostaglandin D<sub>2</sub> from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 665 LP - 672 DO - 10.1124/jpet.108.141333 VL - 327 IS - 3 AU - Dean Papaliodis AU - William Boucher AU - Duraisamy Kempuraj AU - Margaret Michaelian AU - Adams Wolfberg AU - Michael House AU - Theoharis C. Theoharides Y1 - 2008/12/01 UR - http://jpet.aspetjournals.org/content/327/3/665.abstract N2 - 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 &lt; 0.05), 90 and 50% (n = 3, p &lt; 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. The American Society for Pharmacology and Experimental Therapeutics ER -