Nicotinic Acid-Induced Flushing Is Mediated by Activation of Epidermal Langerhans Cells

@article{Beny2006NicotinicAF,
  title={Nicotinic Acid-Induced Flushing Is Mediated by Activation of Epidermal Langerhans Cells},
  author={Zolt{\'a}n Beny{\'o} and Andreas Gille and Clare L. Bennett and Bj{\"o}rn E. Clausen and Stefan Offermanns},
  journal={Molecular Pharmacology},
  year={2006},
  volume={70},
  pages={1844 - 1849}
}
The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been shown to be mediated by the nicotinic acid receptor GPR109A and to involve the formation of vasodilatory prostanoids. However, the cellular mechanisms underlying this short-term effect are unknown… Expand
Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice.
TLDR
The early and late phases of the GPR109A-mediated cutaneous flushing reaction involve different epidermal cell types and prostanoid-forming enzymes, which will help to guide new efficient approaches to mitigate nicotinic acid-induced flushing and may help to exploit the potential antipsoriatic effects of G PR109A agonists in the skin. Expand
Role of HCA₂ (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin.
TLDR
Recent progress in the understanding of the mechanisms underlying HCA₂-mediated flushing is summarized, strategies to mitigate it are described and the potential link between flushing, HCA ₂ and the anti-psoriatic effects of FAE is discussed. Expand
Potential role for epidermal Langerhans cells in nicotinic acid-induced vasodilatation in the mouse
TLDR
Results suggest that Langerhans cells are responsible for nicotinic acid-induced vasodilatation, and non-specific effects of hydrocortisone on arachidonic acid metabolism are excluded. Expand
beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.
TLDR
The data suggest that the adverse side effect of cutaneous flushing is mediated by beta-arrestin1, but lowering of serum free fatty acid levels is not, and G protein-biased ligands that activate GPR109A in a beta-Arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia. Expand
Nicotinic Acid Activates the Capsaicin Receptor TRPV1: Potential Mechanism for Cutaneous Flushing
TLDR
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. Expand
Nicotinic Acid Receptor Agonists Differentially Activate Downstream Effectors*
TLDR
A number of GPR109A pyrazole agonists are identified that are capable of fully inhibiting lipolysis in vitro and in vivo and not only fail to elicit a flushing response but can antagonize the ability of nicotinic acid to elicite a flush response in vivo. Expand
Nicotinic Acid Activates the Capsaicin Receptor TRPV1Significance
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.Expand
The role of nicotinic acid metabolites in flushing and hepatotoxicity.
  • R. Stern
  • Medicine
  • Journal of clinical lipidology
  • 2007
TLDR
The role of metabolism of nicotinic acid in the production of flushing and hepatotoxicity is reviewed and the suggestion that nicotinamide metabolites produce hepatot toxicity is not supported by any data. Expand
Nicotinic acid: pharmacological effects and mechanisms of action.
TLDR
New drugs acting via the nicotinic acid receptor or related receptors, as well as new co-medications that suppress unwanted effects of nicotinIC acid, will most likely be introduced as new therapeutic options in the treatment of dyslipidemia and the prevention of cardiovascular diseases. Expand
Nicotinic acid: recent developments
TLDR
Recent developments suggest that the niacin receptor GPR109A is involved in flushing, but it does not explain multiple actions of niacIn, and actions ofniacin on diacylglycerolacyl transferase 2, ATP synthase β chain, and redox state may explain the multiple actions. Expand
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TLDR
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It is shown that the orphan G-protein-coupled receptor, 'protein upregulated in macrophages by interferon-γ' (mouse PUMA-G, human HM74), is highly expressed in adipose tissue and is a nicotinic acid receptor. Expand
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