The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli.
The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli.
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DOI：
10.1053/j.gastro.2009.07.048
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发表时间：
2009-12
期刊：
影响因子：
29.4
通讯作者：
Blackshaw LA
中科院分区：
文献类型：
--
作者：
Brierley SM;Hughes PA;Page AJ;Kwan KY;Martin CM;O'Donnell TA;Cooper NJ;Harrington AM;Adam B;Liebregts T;Holtmann G;Corey DP;Rychkov GY;Blackshaw LA
瞬时受体电位（TRP）通道家族包括内脏感觉神经元的机械和化学刺激换能器。TRPA1与炎性疼痛有关；它与g蛋白偶联受体相互作用，但对其在胃肠道中的作用知之甚少。来自胃肠道的感觉信息通过5种传入亚型沿着3条通路传导。采用定量RT-PCR、逆行标记和原位杂交的方法，对野生型和TRPA1 - / -小鼠的结节和背根神经节（DRG）进行了分析，其神经元支配胃肠道的3个不同区域。免疫组织化学分析远端结肠切片。进行了体外电生理和药理学研究，并测量了结肠膨胀和内脏运动反应。三硝基苯磺酸诱导结肠炎。TRPA1是迷走神经、内脏和骨盆传入神经特定亚群正常机械和化学感觉功能所必需的。TRPA1−/−小鼠对有害结肠膨胀的行为反应显著降低。TRPA1激动剂引起机械超敏反应，结肠炎小鼠的机械超敏反应增加。缓激肽和辣椒素激活结肠传入，模拟组织损伤的效应；野生型和TRPA1−/−小鼠对这两种刺激有相似的直接反应。在缓激肽激活后，野生型传入神经具有增加的机械敏感性，而在辣椒素暴露后，机械敏感性降低-这些变化在TRPA1 - / -小鼠中不存在。蛋白酶受体(2)活化与TRPA1之间没有明显的相互作用。这些发现证明了TRPA1在正常和炎症的机械感觉功能和内脏伤害感受中的作用是以前未被认识到的。
The transient receptor potential (TRP) channel family includes transducers of mechanical and chemical stimuli for visceral sensory neurons. TRPA1 is implicated in inflammatory pain; it interacts with G-protein-coupled receptors, but little is known about its role in the gastrointestinal (GI) tract. Sensory information from the GI tract is conducted via 5 afferent subtypes along 3 pathways. Nodose and dorsal root ganglia (DRG) whose neurons innnervate 3 different regions of the GI tract were analyzed from wild-type and TRPA1−/− mice using quantitative RT-PCR, retrograde labeling, and in situ hybridization. Distal colon sections were analyzed by immunohistochemistry. In vitro electrophysiology and pharmacology studies were performed and colorectal distension and visceromotor responses were measured. Colitis was induced by administration of trinitrobenzene sulphonic acid. TRPA1 is required for normal mechano- and chemosensory function in specific subsets of vagal, splanchnic and pelvic afferents. The behavioral responses to noxious colonic distension were substantially reduced in TRPA1−/− mice. TRPA1 agonists caused mechanical hypersensitivity, which increased in mice with colitis. Colonic afferents were activated by bradykinin and capsaicin, which mimic effects of tissue damage; wild-type and TRPA1 −/− mice had similar direct responses to these 2 stimuli. After activation by bradykinin, wild-type afferents had increased mechanosensitivity whereas after capsaicin exposure, mechanosensitivity was reduced—these changes were absent in TRPA1−/− mice. No interaction between protease receptor (2) activation and TRPA1 was evident. These findings demonstrate a previously unrecognized role for TRPA1 in normal and inflamed mechanosensory function and nociception within the viscera.
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影响因子：
29.4
作者：
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通讯作者：
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