Chemical, Biological and Radiological (CBR) Division, Defence Science and Technology Laboratory (Dstl), Salisbury, UK.
Hum Exp Toxicol. 2020 Jan;39(1):14-36. doi: 10.1177/0960327119877460. Epub 2019 Oct 2.
The transient receptor potential ankyrin 1 (TRPA1) ion channel is a sensor for irritant chemicals, has ancient lineage, and is distributed across animal species including humans, where it features in many organs. Its activation by a diverse panel of electrophilic molecules (TRPA1 agonists) through electrostatic binding and/or covalent attachment to the protein causes the sensation of pain. This article reviews the species differences between TRPA1 channels and their responses, to assess the suitability of different animals to model the effects of TRPA1-activating electrophiles in humans, referring to common TRPA1 activators (exogenous and endogenous) and possible mechanisms of action relating to their toxicology. It concludes that close matching of in vitro and in vivo models will help optimise the identification of relevant biochemical and physiological responses to benchmark the efficacy of potential therapeutic drugs, including TRPA1 antagonists, to counter the toxic effects of those electrophiles capable of harming humans. The analysis of the species issue provided should aid the development of medical treatments to counter poisoning by such chemicals.
瞬时受体电位锚蛋白 1（TRPA1）离子通道是一种感应刺激性化学物质的传感器，具有古老的进化谱系，分布在包括人类在内的各种动物物种中，在许多器官中都有其特征。其通过静电结合和/或共价附着于蛋白质，被多种亲电子分子（TRPA1 激动剂）激活，从而引起疼痛感觉。本文综述了 TRPA1 通道及其反应的种间差异，以评估不同动物作为人类 TRPA1 激活亲电子体效应模型的适宜性，涉及常见的 TRPA1 激活剂（外源性和内源性）以及与其毒理学相关的可能作用机制。结论认为，体外和体内模型的紧密匹配将有助于优化对相关生化和生理反应的识别，以基准评估潜在治疗药物（包括 TRPA1 拮抗剂）的疗效，以对抗那些能够伤害人类的亲电子体的毒性作用。提供的种间问题分析应有助于开发治疗此类化学物质中毒的医疗方法。
