French Shauna L, Hamilton Justin R
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
Br J Pharmacol. 2016 Oct;173(20):2952-65. doi: 10.1111/bph.13455. Epub 2016 Mar 10.
Protease-activated receptors are a family of four GPCRs (PAR1-PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first-in-class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.
蛋白酶激活受体是一类包含四个G蛋白偶联受体（PAR1 - PAR4）的家族，具有许多独特的特性。在首个PAR被发现近二十五年后，一种靶向该受体的拮抗剂已被批准用于人类。一流的PAR1拮抗剂沃拉帕沙于2014年在美国被批准用于预防有心肌梗死病史或外周动脉疾病患者的血栓性心血管事件。这些最新进展表明了操纵PAR功能的临床潜力。虽然许多工作旨在揭示PAR1的功能，在较小程度上也涉及PAR2，但对于PAR3和PAR4的药理学和生理学了解相对较少。最近的研究已开始开发详细研究PAR4功能所需的药理学和遗传学工具，目前也有越来越多的证据表明PAR4在疾病环境中的功能。在本综述中，我们详细阐述了PAR4的发现、结构、药理学、生理意义和治疗潜力。相关文章 本文是关于G蛋白偶联受体分子药理学主题部分的一部分。要查看本部分的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc。
