Faculty of Pharmacy, University of Sydney, NSW, Australia.
School of Life Sciences, University of Technology Sydney, NSW, Australia; Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.
Pulm Pharmacol Ther. 2018 Apr;49:75-87. doi: 10.1016/j.pupt.2018.01.008. Epub 2018 Jan 31.
Arachidonic acid is metabolized by cyclooxygenases (COX-1 and COX-2) into various prostanoids which exert different functions in mammalian physiology. One of these prostanoids, prostaglandin E (PGE), interacts with four different G protein-coupled receptors, named EP, EP, EP and EP, to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE is responsible for a large variety of beneficial and disadvantageous effects. We have recently achieved a greater understanding of the biology of prostanoid E receptors and the potential for specific drug targeting with the advent of potent and selective EP receptor agonists and antagonists. This has important implications for lung health and disease as PGE-mediated EP receptor activation impacts upon migration of airway smooth muscle cells, airway microvascular leak, tone regulation of pulmonary blood vessels, mast cell degranulation, bronchodilatation, cough, angiogenesis and airway inflammation, to name a few. In this review, we overview the EP receptor family and the related signalling pathways, summarize a variety of EP receptor agonists and antagonists, provide an overview of pharmacological tools used to implicate EP receptor function in the context of respiratory health and disease and finally highlight some of the more selective pharmacological reagents that have recently been developed. The availability of selective pharmacological agonists and antagonists for the distinct EP receptors, as well as the development of specific prostanoid receptor knock-out mice, offer hitherto unattainable opportunities for achieving an in depth understanding of the role and function of PGE in respiratory disease and the exciting potential of targeting EP receptors more broadly.
花生四烯酸被环氧化酶（COX-1 和 COX-2）代谢为各种前列腺素，这些前列腺素在哺乳动物生理学中发挥不同的功能。这些前列腺素之一，前列腺素 E（PGE），与四个不同的 G 蛋白偶联受体（EP、EP、EP 和 EP）相互作用，启动不同的下游信号通路。前列腺素受体在全身不同组织中广泛表达，PGE 负责多种有益和不利的影响。随着强效和选择性 EP 受体激动剂和拮抗剂的出现，我们最近对前列腺素 E 受体的生物学和特定药物靶向的潜力有了更深入的了解。这对肺部健康和疾病具有重要意义，因为 PGE 介导的 EP 受体激活会影响气道平滑肌细胞的迁移、气道微血管渗漏、肺血管张力调节、肥大细胞脱颗粒、支气管扩张、咳嗽、血管生成和气道炎症等。在这篇综述中，我们概述了 EP 受体家族和相关信号通路，总结了各种 EP 受体激动剂和拮抗剂，概述了用于在呼吸健康和疾病背景下阐明 EP 受体功能的药理学工具，并最后强调了最近开发的一些更具选择性的药理学试剂。具有不同 EP 受体的选择性药理学激动剂和拮抗剂的可用性，以及特定前列腺素受体敲除小鼠的开发，为深入了解 PGE 在呼吸疾病中的作用和功能以及更广泛地靶向 EP 受体提供了前所未有的机会。
