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.
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 D(2) (PGD(2)) release from macrophages. Here, we show that methylnicotinate induces significant PGD(2) release from human mast cells and serotonin from human platelets. Intradermal injection of methylnicotinate induces rat skin vasodilation and vascular permeability. Niacin increases plasma PGD(2) and serotonin in a rat model of flush. The phenothiazine prochlorperazine, the H(1), 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 PGD(2) and serotonin, suggesting that drugs other than ASA are required to effectively inhibit niacin-induced flush.
Papaliodis
Dean
D
Department of Pharmacology and Experimental Therapeutics, Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA.
Boucher
William
W
Kempuraj
Duraisamy
D
Michaelian
Margaret
M
Wolfberg
Adams
A
House
Michael
M
Theoharides
Theoharis C
TC
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002199:Capillary Permeability; D005483:Flushing / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D023421:Models, Animal; D009525:Niacin / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000097:blood / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D012867:Skin / Q000098:blood supply; D014664:Vasodilation
D009525:Niacin; D012701:Serotonin; D015230:Prostaglandin D2