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临床意义：內容擴充

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'''瞬态感受器阳离子电压通道，子分类 M，成员 8（TRPM8）'''，是一种存在于人类身上的蛋白质，化学式为：C5893H9102O1694N1518S49<ref>{{Cite web |title=Expasy - ProtParam |url=https://web.expasy.org/cgi-bin/protparam/protparam_bis.cgi?Q7Z2W7@1-1104@ |website=web.expasy.org |access-date=2025-09-16}}</ref>，由''TRPM8''[[基因]]所编码，它又被称为'''冷及薄荷醇感受器1（CMR1）'''<ref name="pmid16382100">{{cite journal | author = Clapham DE, Julius D, Montell C, Schultz G | title = International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels | journal = Pharmacological reviews | volume = 57 | issue = 4 | pages = 427–50 | pmid = 16382100 | doi = 10.1124/pr.57.4.6 | url = |date=December 2005}}</ref>。

==功能==
TRPM8是一种[[离子通道]]，在活化时它允许[[钠]]离子、[[钾]]离子、铯离子和钙离子进入细胞内，这导致[[细胞]]的[[去极化]]以及产生一个[[动作电位]]，并最终将导致生物感受到冷的感觉。

在感觉神经元上会表达这种TRPM8蛋白，该蛋白会被温度降低，或者诸如[[薄荷醇]]、[[依色林]](冰素)等冷感剂激活。对于TRPM8来说，WS-12和CPS-369是最具选择性的激动剂<ref>{{cite journal |author=Sherkheli M.A. et al. |title=Selective TRPM8 agonists: a novel group of neurophathic analgesics |journal=FEBS Journal |volume=274 |issue=s1 |pages=232 |year=2007 |month= |pmid= |doi=10.1111/j.0014-2956.2007.05861_4.x |url=}}</ref><ref name="pmid18930858">{{cite journal | author = Sherkheli M.A., G G, Ak VE, Jf D, H H | title = Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels | journal = Pak J Pharm Sci | volume = 21 | issue = 4 | pages = 370–8 | pmid = 18930858 | doi = | url = http://www.pjps.pk/ | issn = | date = October 2008 | access-date = 2011-06-15 | archive-date = 2011-10-05 | archive-url = https://web.archive.org/web/20111005173304/http://www.pjps.pk/ | dead-url = no }}</ref>。

此外，在[[前列腺]]、[[肺]]、[[膀胱]]等处的细胞上也表达TRPM8蛋白，但其功能和作用并不是十分了解。

==临床意义==
传统意义上，冷敷是一种常见的对外伤引起的疼痛的缓解方法，然而长期以来人們對这种鎮痛作用的机理并没有清晰的认识，直到TRPM8蛋白被发现。

有研究发现TRPM8会被如[[薄荷醇]]的冷感剂所激活，也可以在周围环境温度低于大约26[[摄氏度|°C]]时被激活，这表明它是导致[[传入神经]]中的初级感觉神经元能感受到冷刺激的原因<ref name="pmid17538622">{{cite journal |author=Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D |title=The menthol receptor TRPM8 is the principal detector of environmental cold. |journal=Nature |volume=448 |issue= 7150|pages=204–208 |year=2007 |pmid=17538622 |doi=10.1038/nature05910 |url=https://archive.org/details/sim_nature-uk_2007-07-12_448_7150/page/204}}</ref> 。

另有独立的研究发现，缺乏TRPM8基因的老鼠对于感知[[冷]]有严重的障碍<ref name="pmid17705869">{{cite journal |author=Daniels RL, McKemy DD |title=Mice left out in the cold: commentary on the phenotype of TRPM8-nulls |journal=Mol Pain |volume=3 |issue= 1|pages=23 |year=2007 |pmid=17705869 |pmc=1988789 |doi=10.1186/1744-8069-3-23 |url=}}</ref>。这些动物也很明显地缺乏许多与冷感出发的相关能力，包括对低温、化学冷感、损伤导致冷敏感以及冷敷镇痛等能力。它们对于深入观察和冷刺激及疼痛刺激有关的化学分子信号路径，提供了非常大的帮助。许多大学和医药公司的研究小组正在积极地寻找与TRPM8有选择性的[[配体]]，以用于生产新一代的[[末梢神经疾病]]镇痛药。有趣的是，低浓度的TRPM8激动剂如薄荷醇及冰素等，在特定情况下可以起到镇痛作用<ref name="pmid16920620">{{cite journal | author = Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC, Fleetwood-Walker SM, Mitchell R | title = Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain | journal = Current biology : CB | volume = 16 | issue = 16 | pages = 1591–605 | pmid = 16920620 | doi = 10.1016/j.cub.2006.07.061 | url = |date=August 2006}}</ref>。然而在健康志愿者身上的实验表明，在高浓度剂量的情况下会导致冷致痛感及机械痛感<ref name="pmid14985268">{{cite journal | author = Wasner G, Schattschneider J, Binder A, Baron R | title = Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors | journal = Brain : a journal of neurology | volume = 127 | issue = Pt 5 | pages = 1159–71 | pmid = 14985268 | doi = 10.1093/brain/awh134 | url = |date=May 2004}}</ref>。

对[[基因剔除小鼠|剔除TRPM8的实验鼠]]的研究，不仅仅表明TRPM8对于冷感是至关重要的，还发现TRPM8在老鼠神经痛感模型中，对于冷致痛感及机械痛感同样是重要的<ref name="pmid17481392">{{cite journal | author = Colburn RW, Lubin ML, Stone DJ Jr, Wang Y, Lawrence D, D'Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N | title = Attenuated cold sensitivity in TRPM8 null mice | journal = Neuron | volume = 54 | issue = 3 | pages = 379–86 | pmid = 17481392 | doi = 10.1016/j.neuron.2007.04.017 | url = |date=May 2007}}</ref>。此外，近期的研究表明，TRPM8的拮抗剂能在神经及内脏疼痛模型中，有效地反转已经建立起来的痛感<ref name="pmid18562636">{{cite journal | author = Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X | journal = American journal of physiology. Renal physiology | volume = 295 | issue = 3 | pages = F803–10 | pmid = 18562636 | doi = 10.1152/ajprenal.90269.2008 | url = | title = AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome |date=September 2008}}</ref>。

膀胱疼痛综合征和TRPM8基因在膀胱组织上的过度表达是有关联的<ref name="pmid16519806">{{cite journal | author = Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P | title = Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations | journal = BMC urology | volume = 6| pages = 6 | year = 2006 | pmid = 16519806 | pmc = 1420318 | doi = 10.1186/1471-2490-6-6 | url = }}</ref>。此外，许多前列腺癌细胞株也有TRPM8基因过度表达的情况。对此，树突时代（Dendreon）和[[Genentech|基因工程科技股份有限公司]]正在致力研究一种TRPM8激动剂致前列腺癌细胞凋亡的方法<ref name="urlDendreon: Targeting Cancer, Transforming Lives">{{cite web |url=http://investor.dendreon.com/ReleaseDetail.cfm?ReleaseID=174120&Header=News |title=Dendreon: Targeting Cancer, Transforming Lives |author= |authorlink= |coauthors= |date=2005-09-21 |format= |work= |publisher=Dendreon Corporation |pages= |language= |archiveurl=https://web.archive.org/web/20081028185621/http://investor.dendreon.com/ReleaseDetail.cfm?ReleaseID=174120&Header=News |archivedate=2008-10-28 |quote= |accessdate=2008-10-31 |deadurl=yes }}</ref>。

此外，小鼠實驗表明TRPM8基因缺失可恢復微血管功能並減輕慢性腎臟病進展。<ref name="TRPM8CDK">{{Cite journal |last=Huang |first=Jenq-Wen |last2=Chen |first2=Chia-Hui |last3=Tsai |first3=Ming-Tsun |last4=Hu |first4=Po-An |last5=Guo |first5=Bei-Chia |last6=Chen |first6=Wen-Hua |last7=Chen |first7=Hao-Wen |last8=Lee |first8=Tzong-Shyuan |last9=Tarng |first9=Der-Cherng |title=Genetic deletion of TRPM8 channels restores microvascular function and mitigates chronic kidney disease progression |url=https://linkinghub.elsevier.com/retrieve/pii/S0891584925012663 |journal=Free Radical Biology and Medicine |language=en |date=2025-12 |volume=241 |doi=10.1016/j.freeradbiomed.2025.10.252 |access-date=2026-04-25}}
</ref>

==参见==
* {{tsl|en|TRPM|TRPM}}

==引用==
{{Reflist|2}}

==深入阅读==
{{refbegin | 2}}
*{{cite journal | author=Clapham DE, Julius D, Montell C, Schultz G |title=International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. |journal=Pharmacol. Rev. |volume=57 |issue= 4 |pages= 427–50 |year= 2006 |pmid= 16382100 |doi= 10.1124/pr.57.4.6 }}
*{{cite journal | author=Voets T, Owsianik G, Nilius B |title=TRPM8. |journal=Handb Exp Pharmacol |volume= 179|issue= 179 |pages= 329–44 |year= 2007 |pmid= 17217067 |doi= 10.1007/978-3-540-34891-7_20 }}
{{refend}}

== 外部链接 ==
* {{MeshName|TRPM8+protein,+human}}

{{NLM content}}
{{Ion channels|g4}}
[[Category:离子通道]]

TRPM8 - 版本历史

imported>Hycaefsiam：​/* 临床意义 */ 內容擴充

imported>Hycaefsiam：/* 临床意义 */ 內容擴充