Niacin-induced 'Flush' Involves Release of Prostaglandin D2from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model
| Autor: | Duraisamy Kempuraj, Dean Papaliodis, Theoharis C. Theoharides, Michael House, Adams Wolfberg, William Boucher, Margaret Michaelian |
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| Rok vydání: | 2008 |
| Předmět: |
Blood Platelets
Serotonin medicine.medical_specialty Ketanserin Vasodilation Pharmacology Cyproheptadine Biology Niacin Capillary Permeability chemistry.chemical_compound Internal medicine Flushing medicine Animals Humans Serotonin receptor antagonist Mast Cells Skin Prostaglandin D2 digestive oral and skin physiology Antagonist food and beverages Rats Endocrinology chemistry Models Animal Molecular Medicine lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 327:665-672 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | 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, p0.05), 90 and 50% (n = 3, p0.05), 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. |
| Databáze: | OpenAIRE |
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