Involvement of TRPA1 activation in acute pain induced by cadmium in mice.
Involvement of TRPA1 activation in acute pain induced by cadmium in mice.
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DOI：
10.1186/1744-8069-9-7
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发表时间：
2013-02-28
期刊：
影响因子：
3.3
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Miura S;Takahashi K;Imagawa T;Uchida K;Saito S;Tominaga M;Ohta T
镉（Cd）是一种环境污染物，急性暴露于它会引起与呼吸道和胃肠道疼痛和炎症相关的症状，但其潜在机制仍不清楚。TRPA 1是一种在感觉神经元中表达的非选择性阳离子通道，并作为伤害感受受体发挥作用。据报道，一些金属离子如Ca、Mg、Ba和Zn调节TRPA 1通道活性。本研究以体外培养的小鼠背根神经节神经元为研究对象，探讨了镉对神经元的影响，并建立了一个异源表达系统，从分子水平上分析了镉的影响。此外，我们还检查了镉是否会引起体内急性疼痛。在野生型小鼠感觉神经元，镉引起的细胞内钙浓度（[Ca 2 +]i）的升高，抑制外部钙去除和TRPA 1阻滞剂。大多数镉敏感神经元也对肉桂醛（TRPA 1激动剂）敏感，TRPA 1（−/−）小鼠神经元中不存在对镉的[Ca 2 +]i反应。对锌不太敏感的TRPA 1突变通道的异源表达显示镉敏感性减弱。细胞内镉成像显示，镉进入感觉神经元通过TRPA 1。在表达TRPA 1的大鼠胰腺癌细胞（RIN-14 B）中证实了Cd的刺激作用。足底注射镉诱导疼痛相关行为，在TRPA 1（−/−）小鼠中大大减弱。镉通过激活TRPA 1兴奋感觉神经元，引起急性疼痛，其机制可能与锌相似。目前的结果表明，TRPA 1参与了镉的伤害性或炎症效应。
Cadmium (Cd) is an environmental pollutant and acute exposure to it causes symptoms related to pain and inflammation in the airway and gastrointestinal tract, but the underlying mechanisms are still unclear. TRPA1 is a nonselective cation channel expressed in sensory neurons and acts as a nociceptive receptor. Some metal ions such as Ca, Mg, Ba and Zn are reported to modulate TRPA1 channel activity. In the present study, we investigated the effect of Cd on cultured mouse dorsal root ganglion neurons and a heterologous expression system to analyze the effect of Cd at the molecular level. In addition, we examined whether Cd caused acute pain in vivo. In wild-type mouse sensory neurons, Cd evoked an elevation of the intracellular Ca concentration ([Ca2+]i) that was inhibited by external Ca removal and TRPA1 blockers. Most of the Cd-sensitive neurons were also sensitive to cinnamaldehyde (a TRPA1 agonist) and [Ca2+]i responses to Cd were absent in TRPA1(−/−) mouse neurons. Heterologous expression of TRPA1 mutant channels that were less sensitive to Zn showed attenuation of Cd sensitivity. Intracellular Cd imaging revealed that Cd entered sensory neurons through TRPA1. The stimulatory effects of Cd were confirmed in TRPA1-expressing rat pancreatic cancer cells (RIN-14B). Intraplantar injection of Cd induced pain-related behaviors that were largely attenuated in TRPA1(−/−) mice. Cd excites sensory neurons via activation of TRPA1 and causes acute pain, the mechanism of which may be similar to that of Zn. The present results indicate that TRPA1 is involved in the nociceptive or inflammatory effects of Cd.
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影响因子：
5.3
作者：
Ahern, GP;Brooks, IM;Wang, XB
通讯作者：
Wang, XB
影响因子：
4.7
作者：
Dong XP;Wang X;Xu H
通讯作者：
Xu H
锌激活损伤感应TRPA1离子通道。
影响因子：
14.8
作者：
Hu, Hongzhen;Bandell, Michael;Petrus, Matt J.;Zhu, Michael X.;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
DOI：
10.1073/pnas.1200362109
发表时间：
2012-05-08
影响因子：
11.1
作者：
Hoch, Eitan;Lin, Wei;Sekler, Israel
通讯作者：
Sekler, Israel
DOI：
10.1073/pnas.0812675106
发表时间：
2009-05-19
影响因子：
11.1
作者：
Andersson, David A.;Gentry, Clive;Bevan, Stuart
通讯作者：
Bevan, Stuart