MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on September 28, 2006; DOI: 10.1124/mol.106.030833

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.106.030833v1
mol.106.030833v2
70/6/1844    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Benyo, Z.
Right arrow Articles by Offermanns, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Benyo, Z.
Right arrow Articles by Offermanns, S.


Received for publication September 12, 2006.
Revised September 28, 2006.
Accepted for publication September 28, 2006.

Nicotinic acid-induced flushing is mediated by activation of epidermal Langerhans cells

Zoltan Benyo 1, Andreas Gille 1, Claire Bennett 2, Bjorn Clausen 2, Stefan Offermanns 3*

1 University of Heidelberg 2 University of Amsterdam 3 Universitat Heidelberg

* Address correspondence to: E-mail: stefan.offermanns{at}pharma.uni-heidelberg.de

Abstract

The anti-dyslipidemic 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 acute effect are unknown. Here we show that epidermal Langerhans cells are essential for the cutaneous flushing response induced by nicotinic acid. Langerhans cells respond with an increase in [Ca2+]i to nicotinic acid and express prostanoid synthases required for the formation of the vasodilatory prostanoids prostaglandin E2 and prostaglandin D2. Depletion of epidermal Langerhans cells but not of macrophages or dendritic cells abrogates nicotinic acid induced flushing. These data unexpectedly identify epidermal Langerhans cells as essential mediators of nicotinic acid induced flushing and may help to generate new strategies to suppress the unwanted effects of nicotinic acid. In addition, our results suggest that Langerhans cells besides their immunological roles are also involved in the local regulation of dermal blood flow.


Key words: Eicosanoids, Leukocytes/Mast cells, Knockout, Cholesterol metabolism/lipoproteins


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. G. Richman, M. Kanemitsu-Parks, I. Gaidarov, J. S. Cameron, P. Griffin, H. Zheng, N. C. Guerra, L. Cham, D. Maciejewski-Lenoir, D. P. Behan, et al.
Nicotinic Acid Receptor Agonists Differentially Activate Downstream Effectors
J. Biol. Chem., June 22, 2007; 282(25): 18028 - 18036.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics