HCA₂（GPR109A）在烟酸和富马酸酯对皮肤作用中的作用。

Role of HCA₂ (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin.

机构信息

Molecular Pharmacology, GIGA-Signal Transduction Unit, University of Liège, CHU B34, 4000 Liège, Belgium.

出版信息

Pharmacol Ther. 2012 Oct;136(1):1-7. doi: 10.1016/j.pharmthera.2012.06.003. Epub 2012 Jun 26.

DOI:10.1016/j.pharmthera.2012.06.003

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.

摘要

烟酸（NA）和富马酸酯（FAE），如单甲基富马酸酯或二甲基富马酸酯，是一类会引起皮肤反应（称为潮红）的药物，这是它们的副作用之一。NA 通过其抗血脂异常活性和涉及免疫细胞的脂质非依赖性机制来降低动脉粥样硬化的进展，而 FAE 通过尚不清楚的机制来治疗银屑病。NA 和 FAE 都会通过激活表皮细胞中的 G 蛋白偶联受体（GPCR）羟基羧酸受体 2（HCA₂，GPR109A）来引起潮红。虽然 NA 的预期作用至少部分也是通过 HCA₂ 介导的，但目前尚不清楚该受体是否也参与了 FAE 的抗银屑病作用。HCA₂ 介导的这些药物的潮红反应涉及朗格汉斯细胞和角质形成细胞通过 COX-1 在朗格汉斯细胞和 COX-2 在角质形成细胞中合成前列腺素 D₂ 和 E₂。这篇综述总结了 HCA₂ 介导的潮红反应机制方面的最新进展，描述了减轻潮红反应的策略，并讨论了潮红、HCA₂ 和 FAE 的抗银屑病作用之间的潜在联系。