Nicotinic acid activates the capsaicin receptor TRPV1: potential mechanism for cutaneous flushing

Ma, Linlin, Lee, Bo Hyun, Mao, Rongrong, Cai, Anping, Jia, Yunfang, Clifton, Heather, Schaefer, Saul, Xu, Lin and Zheng, Jie (2014) Nicotinic acid activates the capsaicin receptor TRPV1: potential mechanism for cutaneous flushing. Arteriosclerosis, Thrombosis, and Vascular Biology, 34 6: 1272-1280. doi:10.1161/ATVBAHA.113.303346

Author Ma, Linlin
Lee, Bo Hyun
Mao, Rongrong
Cai, Anping
Jia, Yunfang
Clifton, Heather
Schaefer, Saul
Xu, Lin
Zheng, Jie
Title Nicotinic acid activates the capsaicin receptor TRPV1: potential mechanism for cutaneous flushing
Journal name Arteriosclerosis, Thrombosis, and Vascular Biology   Check publisher's open access policy
ISSN 1524-4636
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1161/ATVBAHA.113.303346
Volume 34
Issue 6
Start page 1272
End page 1280
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams and Wilkins
Language eng
Formatted abstract
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.
Keyword Cardiovascular diseases
Ion channels
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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