Morrow J D, Awad J A, Oates J A, Roberts L J
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Invest Dermatol. 1992 May;98(5):812-5. doi: 10.1111/1523-1747.ep12499963.
Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D2. However, the site from which PGD2 is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD2 locally from skin and the possibility that skin may be a major contributor to the release of PGD2 when niacin is administered by mouth. Topical administration of methylnicotinate (10(-1) M) to the forearms of human volunteers resulted in 58- to 122-times increases in levels of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD2 was released from the site of methylnicotinate application. The release of PGD2 in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10(-3) to 10(-1) M. The release of PGD2 was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell. Following oral ingestion of niacin, levels of PGD2 in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin of the same arm. This finding indicates that the skin is a major site from which PGD2 is released following oral ingestion of niacin. These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD2 from a niacin responsive cell that resides in the skin.
口服能降低血清胆固醇水平的药理剂量烟酸（尼克酸）会使人体出现强烈潮红。我们最近发现，摄入烟酸后的血管舒张是由于前列腺素（PG）D2的释放。然而，PGD2的释放部位尚不清楚。此前已表明，局部应用烟酸甲酯会导致局部皮肤红斑。因此，我们研究了局部应用烟酸甲酯是否会使皮肤局部释放PGD2，以及口服烟酸时皮肤是否可能是PGD2释放的主要来源。对人类志愿者的前臂局部应用烟酸甲酯（10⁻¹ M），导致从前臂静脉抽取的血液中PGD2水平升高58至122倍，PGD2代谢物9α,11β - PGF2水平升高25至33倍。同时从对侧手臂静脉抽取的血液中未发现PGD2和9α,11β - PGF2水平升高，这表明PGD2是从烟酸甲酯应用部位释放的。在10⁻³至10⁻¹ M的浓度范围内，对局部应用烟酸甲酯的反应中PGD2的释放呈剂量依赖性。PGD2的释放未伴随组胺的释放，这表明PGD2不是从肥大细胞释放的。口服烟酸后，引流皮肤的浅表静脉血中PGD2水平比供应同一只手臂皮肤的动脉血中水平高14至1200倍。这一发现表明，皮肤是口服烟酸后PGD2释放的主要部位。因此，这些研究表明，口服烟酸后发生的皮肤血管舒张主要是由于驻留在皮肤中的对烟酸有反应的细胞释放PGD2所致。
