Papaliodis Dean, Boucher William, Kempuraj Duraisamy, Michaelian Margaret, Wolfberg Adams, House Michael, Theoharides Theoharis C
Department of Pharmacology and Experimental Therapeutics, Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA.
J Pharmacol Exp Ther. 2008 Dec;327(3):665-72. doi: 10.1124/jpet.108.141333. Epub 2008 Sep 10.
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.
烟酸可降低血清胆固醇、低密度脂蛋白和甘油三酯，并能提高高密度脂蛋白。然而，大多数患者会出现皮肤发热和血管扩张（潮红）。乙酰水杨酸（ASA）可减轻这种潮红，推测是通过减少巨噬细胞释放前列腺素D2（PGD2）来实现的。在此，我们发现烟酸甲酯可诱导人肥大细胞释放大量PGD2，并使人血小板释放5-羟色胺。皮内注射烟酸甲酯可诱导大鼠皮肤血管扩张和血管通透性增加。在大鼠潮红模型中，烟酸可增加血浆PGD2和5-羟色胺水平。在该动物模型中，吩噻嗪类药物丙氯拉嗪、H1、5-羟色胺受体拮抗剂赛庚啶以及特异性5-羟色胺受体-2A拮抗剂酮色林分别可将烟酸诱导的体温升高抑制90%（n = 5，p < 0.05）、90%和50%（n = 3，p < 0.05）以及85%（n = 6，p = 0.0008）。这些结果表明，烟酸诱导的潮红涉及PGD2和5-羟色胺两者，提示除了ASA之外，还需要其他药物来有效抑制烟酸诱导的潮红。
