Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin
Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin
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DOI：
10.1016/s0896-6273(04)00150-3
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发表时间：
2004-03-25
期刊：
影响因子：
16.2
通讯作者：
Patapoutian, A
中科院分区：
文献类型：
--
作者：
Bandell, M;Story, GM;Patapoutian, A
哺乳动物瞬时受体电位（TRP）离子通道的六个成员响应于不同的温度阈值。天然化合物辣椒素和薄荷醇分别激活有毒的热敏TRPV1和冷敏TRPM8。辣椒素和薄荷醇的灼烧感和凉爽感表明这些离子通道介导了温度感觉。我们发现，除了有毒的寒冷，肉桂油，冬青油，菜籽油，芥末油和生姜中存在的辛辣天然化合物都激活TRPA1（ANKTM 1）。缓激肽是一种通过其G蛋白偶联受体起作用的炎性肽，也激活TRPA1。我们进一步表明，磷脂酶C是TRPA1激活的重要信号成分。肉桂醛是最具特异性的TRPA1激活剂，可兴奋小鼠中高度富集冷敏感神经元的感觉神经元亚群并激发伤害性行为。总的来说，这些数据表明，TRPA1激活elevates疼痛的感觉，并提供了一个潜在的分子模型，为什么有害的寒冷可以矛盾地被视为灼热的疼痛。
Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.