Peters Terence, Henry Peter J
School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.
Br J Pharmacol. 2009 Oct;158(4):1017-33. doi: 10.1111/j.1476-5381.2009.00449.x.
Protease-activated receptors (PARs) are a novel family of G protein-coupled receptors. Signalling through PARs typically involves the cleavage of an extracellular region of the receptor by endogenous or exogenous proteases, which reveals a tethered ligand sequence capable of auto-activating the receptor. A considerable body of evidence has emerged over the past 20 years supporting a prominent role for PARs in a variety of human physiological and pathophysiological processes, and thus substantial attention has been directed towards developing drug-like molecules that activate or block PARs via non-proteolytic pathways. PARs are widely expressed within the respiratory tract, and their activation appears to exert significant modulatory influences on the level of bronchomotor tone, as well as on the inflammatory processes associated with a range of respiratory tract disorders. Nevertheless, there is debate as to whether the principal response to PAR activation is an augmentation or attenuation of airways inflammation. In this context, an important action of PAR activators may be to promote the generation and release of prostanoids, such as prostglandin E(2), which have well-established anti-inflammatory effects in the lung. In this review, we primarily focus on the relationship between PARs, prostaglandins and inflammatory processes in the lung, and highlight their potential role in selected respiratory tract disorders, including pulmonary fibrosis, asthma and chronic obstructive pulmonary disease.
蛋白酶激活受体（PARs）是一类新型的G蛋白偶联受体。通过PARs进行信号传导通常涉及内源性或外源性蛋白酶对受体胞外区域的切割，从而暴露出一个能够自动激活受体的拴系配体序列。在过去20年里，大量证据表明PARs在多种人类生理和病理生理过程中发挥着重要作用，因此人们将大量注意力投向开发能够通过非蛋白水解途径激活或阻断PARs的类药物分子。PARs在呼吸道中广泛表达，其激活似乎对支气管运动张力水平以及与一系列呼吸道疾病相关的炎症过程产生显著的调节作用。然而，关于PAR激活的主要反应是增强还是减弱气道炎症存在争议。在这种情况下，PAR激活剂的一个重要作用可能是促进前列腺素类物质的生成和释放，如前列腺素E(2)，其在肺部具有公认的抗炎作用。在这篇综述中，我们主要关注PARs、前列腺素与肺部炎症过程之间的关系，并强调它们在包括肺纤维化、哮喘和慢性阻塞性肺疾病在内的特定呼吸道疾病中的潜在作用。
