Nicotinic Acid Activates the Capsaicin Receptor TRPV1 Potential Mechanism for Cutaneous Flushing
文献类型：期刊论文
| 作者 | Ma LL1,4; Lee BH1; Mao RR3; Cai AP3; Jia YF3; Clifton H2; Schaefer S2; Xu L3; Zheng J[*]1 |
| 刊名 | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
 |
| 出版日期 | 2014 |
| 卷号 | 34期号:6页码:1272-1280 |
| 关键词 | cardiovascular diseases ion channels lipoproteins vasodilation |
| 通讯作者 | jzheng@ucdavis.edu |
| 合作状况 | 其它 |
| 英文摘要 | Objective Nicotinic acid (also known as niacin or vitamin B3), widely used to treat dyslipidemias, represents an effective and safe means to reduce the risk of mortality from cardiovascular disease. Nonetheless, a substantial fraction of patients discontinue treatment because of a strong side effect of cutaneous vasodilation, commonly termed flushing. In the present study, we tested the hypothesis that nicotinic acid causes flushing partially by activating the capsaicin receptor TRPV1, a polymodal cellular sensor that mediates the flushing response on consumption of spicy food. Approach and Results We observed that the nicotinic acid-induced increase in blood flow was substantially reduced in Trpv1(-/-) knockout mice, indicating involvement of the channel in flushing response. Using exogenously expressed TRPV1, we confirmed that nicotinic acid at submillimolar to millimolar concentrations directly and potently activates TRPV1 from the intracellular side. Binding of nicotinic acid to TRPV1 lowers its activation threshold for heat, causing channel opening at physiological temperatures. The activation of TRPV1 by voltage or ligands (capsaicin and 2-aminoethoxydiphenyl borate) is also potentiated by nicotinic acid. We further demonstrated that nicotinic acid does not compete directly with capsaicin but may activate TRPV1 through the 2-aminoethoxydiphenyl borate activation pathway. Using live-cell fluorescence imaging, we observed that nicotinic acid can quickly enter the cell through a transporter-mediated pathway to activate TRPV1. Conclusions Direct activation of TRPV1 by nicotinic acid may lead to cutaneous vasodilation that contributes to flushing, suggesting a potential novel pathway to inhibit flushing and to improve compliance. |
| 收录类别 | SCI |
| 资助信息 | This work was supported, in part, by National Institutes of Health grant R01NS072377 (to Dr Zheng) and an Australian National Health and Medical Research Council fellowship (to Dr Ma). |
| 语种 | 英语 |
| WOS记录号 | WOS:000335809900024 |
| 公开日期 | 2014-12-19 |
| 源URL | [http://159.226.149.42:8088/handle/152453/8199]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 |
| 作者单位 | 1.Department of Physiology and Membrane Biology,University of California School of Medicine, Davis 2.Division of Cardiovascular Medicine,University of California School of Medicine, Davis 3.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan Province, China 4.Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia |
| 推荐引用方式 GB/T 7714 | Ma LL,Lee BH,Mao RR,et al. Nicotinic Acid Activates the Capsaicin Receptor TRPV1 Potential Mechanism for Cutaneous Flushing[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2014,34(6):1272-1280. |
| APA | Ma LL.,Lee BH.,Mao RR.,Cai AP.,Jia YF.,...&Zheng J[*].(2014).Nicotinic Acid Activates the Capsaicin Receptor TRPV1 Potential Mechanism for Cutaneous Flushing.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,34(6),1272-1280. |
| MLA | Ma LL,et al."Nicotinic Acid Activates the Capsaicin Receptor TRPV1 Potential Mechanism for Cutaneous Flushing".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 34.6(2014):1272-1280. |
入库方式： OAI收割
来源：昆明动物研究所
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