A novel role for TRPM8 in visceral afferent function
A novel role for TRPM8 in visceral afferent function
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DOI：
10.1016/j.pain.2011.01.027
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发表时间：
2011-07-01
期刊：
影响因子：
7.4
通讯作者：
Brierley, Stuart M.
中科院分区：
文献类型：
--
作者：
Harrington, Andrea M.;Hughes, Patrick A.;Brierley, Stuart M.
瞬时受体电位离子通道melastatin亚型8（TRPM 8）被低温和冷却剂（如薄荷醇和icilin）激活。据报道，含有薄荷的化合物可减轻肠过敏症状;然而，其潜在的作用机制尚不清楚。在这里，我们确定了TRPM 8在结肠感觉通路中的作用。激光捕获显微切割，定量逆转录-聚合酶链反应（RT-PCR），免疫荧光和逆行追踪被用来定位TRPM 8结肠初级传入神经元。在体外细胞外单纤维传入记录被用来确定TRPM 8通道激活结肠高阈值传入纤维的化学感觉和机械感觉功能的影响。TRPM 8 mRNA存在于结肠DRG神经元中，而TRPM 8蛋白存在于整个结肠壁的神经纤维上。一个亚群（24%，n = 58）的内脏血清和肠系膜传入测试直接响应icilin（5 μ mol/L）。随后，icilin显着脱敏传入机械刺激（P <0.0001; n = 37）。内脏传入反应icilin，21（33%）也直接响应于TRPV 1激动剂辣椒素（3 μ mol/L），和icilin减少辣椒素的直接化学感觉反应。Icilin也防止机械感觉脱敏和致敏诱导的辣椒素和TRPA 1激动剂AITC（40 μ mol/L），分别。TRPM 8存在于结肠高阈值感觉神经元的选择群体上，其也可以共表达TRPV 1。TRPM 8与TRPV 1和TRPA 1偶联以抑制其下游化学感受和机械感受作用。(C)2011年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n = 58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 mu mol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P < .0001; n = 37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 mu mol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 mu mol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.