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Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush.
- Source :
-
Atherosclerosis [Atherosclerosis] 2007 Jun; Vol. 192 (2), pp. 253-8. Date of Electronic Publication: 2006 Sep 01. - Publication Year :
- 2007
-
Abstract
- Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D2 (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD2 secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD2 secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD2 secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2 secretion. The PGD2 secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 microM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.
- Subjects :
- Aspirin pharmacology
Calcimycin pharmacology
Calcium physiology
Humans
Models, Biological
Niacin antagonists & inhibitors
Nicotinic Acids pharmacology
Tumor Cells, Cultured
Flushing chemically induced
Macrophages drug effects
Macrophages metabolism
Niacin adverse effects
Niacin pharmacology
Prostaglandin D2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9150
- Volume :
- 192
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 16945375
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2006.07.014