Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor
Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor
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DOI：
10.1016/j.taap.2008.04.005
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发表时间：
2008-09-01
影响因子：
3.8
通讯作者：
Gijsen, Harrie J. M.
中科院分区：
文献类型：
--
作者：
Brone, Bert;Peeters, Pieter J.;Gijsen, Harrie J. M.
TRPA1通道被许多刺激性化学物质激活，例如芥子油中存在的烯丙基异硫氰酸酯和大蒜中存在的硫代亚硫酸盐。大多数已知的活性化合物都含有活性的、亲电的化学基团，与TRPA1通道活性部位的半胱氨酸残基发生反应。这种共价修饰导致通道的激活，并已被证明对几个配体是可逆的。常用的泪液气体CN、CR和CS也是刺激性化学物质，在这项研究中，我们证明它们是非常有效和选择性的人类TRPA1受体激活剂。据我们所知，这些是迄今已知的最有效的TRPA1激动剂。识别这些催泪气体的分子靶点可能会打开通过使用TRPA1拮抗剂来减轻催泪气体影响的可能性。此外，这些结果可能有助于了解TRPA1通道的基本知识，该通道作为一个药理靶点正变得越来越重要。(C)2008 Elsevier Inc.保留所有权利。
The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target. (C) 2008 Elsevier Inc. All rights reserved.