Role of HCA₂ (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin.
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| Abstract |
Nicotinic acid (NA) and fumaric acid esters (FAE) such as monomethyl fumarate or dimethyl fumarate are drugs that elicit a cutaneous reaction called flushing as a side effect. NA is used to reduce progression of atherosclerosis through its anti-dyslipidemic activity and lipid-independent mechanisms involving immune cells, whereas FAE are used to treat psoriasis via largely unknown mechanisms. Both, NA and FAE, induce flushing by the activation of the G-protein-coupled receptor (GPCR) Hydroxy-carboxylic acid receptor 2 (HCA₂, GPR109A) in cells of the epidermis. While the wanted effects of NA are at least in part also mediated by HCA₂, it is currently not clear whether this receptor is also involved in the anti-psoriatic effects of FAE. The HCA₂-mediated flushing response to these drugs involves the formation of prostaglandins D₂ and E₂ by Langerhans cells and keratinocytes via COX-1 in Langerhans cells and COX-2 in keratinocytes. This review summarizes recent progress in the understanding of the mechanisms underlying HCA₂-mediated flushing, describes strategies to mitigate it and discusses the potential link between flushing, HCA₂ and the anti-psoriatic effects of FAE.
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| Authors | Julien Hanson, Andreas Gille, Stefan Offermanns |
| Journal | Pharmacology & therapeutics (Pharmacol Ther) Vol. 136 Issue 1 Pg. 1-7 (Oct 2012) ISSN: 1879-016X [Electronic] England |
| PMID | 22743741 (Publication Type: Journal Article, Review) |
| Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
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