Institute of Physiology, University Hospital RWTH Aachen , Aachen , Germany.
Center for Physiology and Pharmacology, Medical University of Vienna , Vienna , Austria.
J Neurophysiol. 2019 Feb 1;121(2):427-443. doi: 10.1152/jn.00524.2018. Epub 2018 Nov 28.
The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in pain-sensing neurons and other tissues and has become a major target in the development of novel pharmaceuticals. A remarkable feature of the channel is its long list of activators, many of which we are exposed to in daily life. Many of these agonists induce pain and inflammation, making TRPA1 a major target for anti-inflammatory and analgesic therapies. Studies in human patients and in experimental animals have confirmed an important role for TRPA1 in a number of pain conditions. Over the recent years, much progress has been made in elucidating the molecular structure of TRPA1 and in discovering binding sites and modulatory sites of the channel. Because the list of published mutations and important molecular sites is steadily growing and because it has become difficult to see the forest for the trees, this review aims at summarizing the current knowledge about TRPA1, with a special focus on the molecular structure and the known binding or gating sites of the channel.
瞬时受体电位锚蛋白 1(TRPA1)离子通道表达于痛觉神经元和其他组织中,已成为新型药物研发的主要靶点。该通道的一个显著特征是其拥有一长串的激活剂,其中许多在日常生活中都会接触到。这些激动剂中的许多会引起疼痛和炎症,这使得 TRPA1 成为抗炎和镇痛治疗的主要靶点。在人类患者和实验动物中的研究证实了 TRPA1 在多种疼痛状况中的重要作用。近年来,在阐明 TRPA1 的分子结构以及发现通道的结合位点和调节位点方面取得了很大进展。由于已发表的突变和重要分子位点的列表在不断增加,并且因为很难看到全貌,所以本篇综述旨在总结目前关于 TRPA1 的知识,特别关注通道的分子结构以及已知的结合或门控位点。