TRPV1 - Wikiwand

TRPV1是指“瞬态感受器电位阳离子通道，子类V，成员1”（transient receptor potential cation channel, subfamily V, member 1），该通道是一个蛋白质，在人类基因中由TRPV1基因所编码^[2]^[3]。这一通道属于一种离子通道，是瞬态电压感受器族中的一员，属于TRPV组（即瞬态感受器电位阳离子通道，子类V）^[4]。

事实速览 瞬态感受器阳离子电压通道子分类V，成员1 [人类], 标识 ...

瞬态感受器阳离子电压通道
子分类V，成员1 [人类]

TRPV1离子通道同源蛋白四聚体的结构模型，其中每一个单体用青、绿、蓝及洋红色分别标出。其中的4,5-二磷酸基磷脂酰肌醇触发配体，根据空间填充模型分别用白、红、橙三种颜色代表碳、氧及磷原子。^[1]其周围的黄色部分为该通道所嵌入其中的双脂膜的示意情形。

标识

代号

TRPV1; DKFZp434K0220; VR1

扩展标识

遗传学：602076 鼠基因：1341787 同源基因：12920 IUPHAR: TRPV1 GeneCards: TRPV1 Gene

基因本体论描述
分子功能	· 感受器活动 · 离子通道活动 · 钙离子通道活动 · 钙离子结合 · 钙调蛋白结合 · 阳离子跨膜转运活动
细胞成分	· 嵌入质膜 · 膜 · 嵌入膜
生物过程	· 体温调节 · 离子转运 · 钙离子转运 · 细胞表面感受器信号转换 · 化学感受器行为 · 酸碱度响应 · 热感响应 · 痛觉感受器 · 温度感应
Sources: Amigo / QuickGO

RNA表达模式

更多表达数据

直系同源体

物种

人类

小鼠

mRNA序列

蛋白序列

基因位置

Chr 17:
3.42 – 3.45 Mb

Chr 11:
73.05 – 73.08 Mb

PubMed查询

[1]

[2]

关闭

TRPV1是一个配体门控非选择性阳离子通道，可以被各种外因性及内因性的物理及化学刺激所激发，例如：温度超过43 °C、pH值低（酸性环境）、内源性大麻素花生四烯酸乙醇胺、N-花生四烯酰基多巴胺以及辣椒素（辣椒的有效成分）。这一通道被发现存在于中枢神经系统及末梢神经系统上，并且涉及痛觉的传递和调制，以及整合各种同疼痛信息^[5]^[6]。

临床意义

针对多种动物的研究发现，阻止TRPV1发挥作用会导致体温上升，包括人类及鼠类。这一发现暗示该通道涉及生物体温调节过程^[7]。而最近，AMG517这种高度针对TRPV1的受体拮抗剂已不再用于临床试验，这是因为它会导致体温升高至无法接受的水平^[8]。近期因类似原因而停用的TRPV1受体拮抗剂还包括GRC 6211以及NGD 8243。另一种化合物SB-705498也被用于类似的临床试验，但其对体温的影响则没有相关报告^[9]。

TRPV1通道蛋白的后期磷酸化翻译修饰，对该通道能否发挥正常功能是至关重要的。近期美国卫生教育与福利部下的国家卫生研究所所发表的报告指出，Cdk5促使的磷酸化修饰，对该通道的配体驱动通道开启的敏感道来说是有重要關係的^[10]。

末梢神经系统

在实验鼠上的试验表明，通过使用针对TRPV1的受体拮抗剂，可以明显减轻炎症反应及神经疼痛的伤害性^[11]。这一结果表明，TRPV1通道是能对辣椒素做出反应的唯一感受器^[12]。

对于人类来说，作用在TRPV1感受器上的药物，应当能用于治疗与多发性硬化症、化疗或者截肢有关的神经性疼痛，也能缓解因组织损伤，如骨关节炎导致的炎症有关的疼痛^[13]。

最近几年，人们才意识到TRPV1通道是体温调节中的一个环节。这是因为人们发现一些针对TRPV1的选择性受体拮抗剂会导致体温升高（高温症），这说明在体内TRPV1通道通过告知大脑应当降温，来不间断的调节着体温^[7] 。如果因某种原因导致TRPV1通道没有及时发出这种降温信号，则体温会不断上升。于此类似的，这也是为什么食用含有辣椒素（针对TRPV1的一种激动剂）的食物会导致流汗——大脑希望通过该方式来降低体温。最近的一个研究表明，在内脏中TRPV1通道也会持续的工作，通过发出降低体温的信号来不断调节体温^[14]。因此，该通道的主要功能被认为是调节体温^[15]。

中枢神经系统

TRPV1通道在高级的中枢神经系统中，也有相应的表达。该通道除了被认为可以用于治疗神经性疼痛之外，还可以治疗其它症状例如焦虑^[16]。此外，该通道似乎还与海马区中的长时程抑制效应有关^[17]。而长时程抑制则会减弱形成新的记忆的能力，于此相反的长时程增强效应则会帮助形成记忆。在突触中形成的抑制与增强模式，则为形成记忆的方式提供了编码。长时程抑制效应及其导致突触链接剪枝的效果，对于形成记忆来说是很重要的。针对实验鼠大脑切片的研究发现，通过热或者辣椒素的刺激可以引发长时程抑制效应，而辣椒素受体阻断剂则能阻碍辣椒素所引起的抑制效应^[17]。因此，正如已经在末梢神经系统中应用TRPV1拮抗剂来缓解疼痛那样，也许将来有可能通过在中枢神经系统中使用这种拮抗剂来治疗一些疾病，例如癫痫。

参见

辣椒素
香草素
大麻素受体
TRPV1拮抗剂的研究与开发

相互作用

TRPV1通道被发现与钙调节蛋白1^[18]、突触结合蛋白9（SYT9）^[19]以及N-乙基马来酰亚胺敏感因子可溶性附着蛋白相关蛋白（SNAPAP）^[19]发生蛋白质-蛋白质相互作用。SNAPAP即SNAP相关蛋白，其中SNAP指可溶性（S）、N-乙基马来酰亚胺敏感因子（N）、附着蛋白（AP）。

引用

[1]
Brauchi, Sebastian; Orta, Gerardo; Mascayano, Carolina; Salazar, Marcelo; Raddatz, Natalia; Urbina, Hector; Rosenmann, Eduardo; Gonzalez-Nilo, Fernando; Latorre, Ramon. Dissection of the components for PIP 2 activation and thermosensation in TRP channels. Proceedings of the National Academy of Sciences. 2007-06-12, 104 (24). ISSN 0027-8424. PMC 1891241 . PMID 17548815. doi:10.1073/pnas.0703420104 （英语）.
[2]
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. October 1997, 389 (6653): 816–24. PMID 9349813. doi:10.1038/39807.
[3]
Xue Q, Yu Y, Trilk SL, Jong BE, Schumacher MA. The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants. Genomics. August 2001, 76 (1-3): 14–20. PMID 11549313. doi:10.1006/geno.2001.6582.
[4]
Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol. Rev. December 2005, 57 (4): 427–50. PMID 16382100. doi:10.1124/pr.57.4.6.
[5]
Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, Marsh K, Bianchi B, McDonald H, Niforatos W, Neelands TR, Moreland RB, Decker MW, Lee CH, Sullivan JP, Faltynek CR. TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J. Neurosci. 2006, 26 (37): 9385–93. PMID 16971522. doi:10.1523/JNEUROSCI.1246-06.2006.
[6]
Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci. U.S.A. 2002, 99 (12): 8400–5. PMID 12060783. doi:10.1073/pnas.122196999.
[7]
Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC. The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J. Neurosci. March 2007, 27 (13): 3366–74. PMID 17392452. doi:10.1523/JNEUROSCI.4833-06.2007.
[8]
Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Alvarez F, Bak A, Darling M, Gore A, Jang GR, Kesslak JP, Ni L, Norman MH, Palluconi G, Rose MJ, Salfi M, Tan E, Romanovsky AA, Banfield C, Davar G. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain. May 2008, 136 (1-2): 202–10. PMID 18337008. doi:10.1016/j.pain.2008.01.024.
[9]
Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain. November 2007, 132 (1-2): 132–41. PMID 17659837. doi:10.1016/j.pain.2007.06.006.
[10]
Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc. Natl. Acad. Sci. U.S.A. January 2007, 104 (2): 660–5. PMC 1752192 . PMID 17194758. doi:10.1073/pnas.0609916104.
[11]
Jhaveri MD, Elmes SJ, Kendall DA, Chapman V. Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats. Eur. J. Neurosci. 2005, 22 (2): 361–70. PMID 16045489. doi:10.1111/j.1460-9568.2005.04227.x.
[12]
Story GM, Cruz-Orengo L. Feel the Burn. American Scientist. 2008, 95 (4): 326–333 [2009-12-03]. ISSN 0003-0996. （原始内容存档于2008-01-19）.
[13]
Gunthorpe MJ, Szallasi A. Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms. Curr. Pharm. Des. 2008, 14 (1): 32–41. PMID 18220816. doi:10.2174/138161208783330754.
[14]
Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL, Bannon AW, Norman MH, Louis JC, Treanor JJ, Gavva NR, Romanovsky AA. Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J. Neurosci. July 2007, 27 (28): 7459–68. PMID 17626206. doi:10.1523/JNEUROSCI.1483-07.2007.
[15]
Gavva NR. Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1. Trends Pharmacol Sci. 2008, 29 (11): 550–557. doi:10.1016/j.tips.2008.08.003.
[16]
Di Marzo V, Starowicz K, Cristino L. TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications. Curr. Pharm. Des. 2008, 14 (1): 42–54. PMID 18220817. doi:10.2174/138161208783330790.
[17]
Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA. TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons. Neuron. 2008, 57 (5): 746–59. PMID 18341994. doi:10.1016/j.neuron.2007.12.027.
[18]
Numazaki, Mitsuko; Tominaga Tomoko; Takeuchi Kumiko; Murayama Namie; Toyooka Hidenori; Tominaga Makoto. Structural determinant of TRPV1 desensitization interacts with calmodulin. Proc. Natl. Acad. Sci. U.S.A. (United States). Jun 2003, 100 (13): 8002–6. ISSN 0027-8424. PMID 12808128. doi:10.1073/pnas.1337252100.
[19]
Morenilla-Palao, Cruz; Planells-Cases Rosa; García-Sanz Nuria; Ferrer-Montiel Antonio. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J. Biol. Chem. (United States). Jun 2004, 279 (24): 25665–72. ISSN 0021-9258. PMID 15066994. doi:10.1074/jbc.M311515200.

深入阅读

Immke DC, Gavva NR. The TRPV1 receptor and nociception. Semin. Cell Dev. Biol. October 2006, 17 (5): 582–91. PMID 17196854. doi:10.1016/j.semcdb.2006.09.004.
Heiner I, Eisfeld J, Lückhoff A. Role and regulation of TRP channels in neutrophil granulocytes.. Cell Calcium. 2004, 33 (5-6): 533–40. PMID 12765698. doi:10.1016/S0143-4160(03)00058-7.
Geppetti P, Trevisani M. Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function.. Br. J. Pharmacol. 2004, 141 (8): 1313–20. PMID 15051629. doi:10.1038/sj.bjp.0705768.
Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.. Pharmacol. Rev. 2006, 57 (4): 427–50. PMID 16382100. doi:10.1124/pr.57.4.6.
Szallasi A, Cruz F, Geppetti P. TRPV1: a therapeutic target for novel analgesic drugs?. Trends in molecular medicine. 2007, 12 (11): 545–54. PMID 16996800. doi:10.1016/j.molmed.2006.09.001.
Pingle SC, Matta JA, Ahern GP. Capsaicin receptor: TRPV1 a promiscuous TRP channel.. Handb Exp Pharmacol. 2007, 179 (179): 155–71. PMID 17217056. doi:10.1007/978-3-540-34891-7_9.
Liddle RA. The role of Transient Receptor Potential Vanilloid 1 (TRPV1) channels in pancreatitis.. Biochim. Biophys. Acta. 2007, 1772 (8): 869–78. PMID 17428642. doi:10.1016/j.bbadis.2007.02.012.

外部链接

醫學主題詞表（MeSH）：Vanilloid+receptors

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分子功能

· 感受器活动

· 离子通道活动
· 钙离子通道活动
· 钙离子结合
· 钙调蛋白结合

· 阳离子跨膜转运活动

细胞成分

· 嵌入质膜

· 膜

· 嵌入膜

生物过程

· 体温调节

· 离子转运
· 钙离子转运
· 细胞表面感受器信号转换
· 化学感受器行为
· 酸碱度响应
· 热感响应
· 痛觉感受器

· 温度感应

Sources: Amigo / QuickGO

临床意义

末梢神经系统

中枢神经系统

相互作用

引用

[1]
Brauchi, Sebastian; Orta, Gerardo; Mascayano, Carolina; Salazar, Marcelo; Raddatz, Natalia; Urbina, Hector; Rosenmann, Eduardo; Gonzalez-Nilo, Fernando; Latorre, Ramon. Dissection of the components for PIP 2 activation and thermosensation in TRP channels. Proceedings of the National Academy of Sciences. 2007-06-12, 104 (24). ISSN 0027-8424. PMC 1891241 . PMID 17548815. doi:10.1073/pnas.0703420104 （英语）.
[2]
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. October 1997, 389 (6653): 816–24. PMID 9349813. doi:10.1038/39807.
[3]
Xue Q, Yu Y, Trilk SL, Jong BE, Schumacher MA. The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants. Genomics. August 2001, 76 (1-3): 14–20. PMID 11549313. doi:10.1006/geno.2001.6582.
[4]
Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol. Rev. December 2005, 57 (4): 427–50. PMID 16382100. doi:10.1124/pr.57.4.6.
[5]
Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, Marsh K, Bianchi B, McDonald H, Niforatos W, Neelands TR, Moreland RB, Decker MW, Lee CH, Sullivan JP, Faltynek CR. TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J. Neurosci. 2006, 26 (37): 9385–93. PMID 16971522. doi:10.1523/JNEUROSCI.1246-06.2006.
[6]
Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci. U.S.A. 2002, 99 (12): 8400–5. PMID 12060783. doi:10.1073/pnas.122196999.
[7]
Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC. The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J. Neurosci. March 2007, 27 (13): 3366–74. PMID 17392452. doi:10.1523/JNEUROSCI.4833-06.2007.
[8]
Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Alvarez F, Bak A, Darling M, Gore A, Jang GR, Kesslak JP, Ni L, Norman MH, Palluconi G, Rose MJ, Salfi M, Tan E, Romanovsky AA, Banfield C, Davar G. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain. May 2008, 136 (1-2): 202–10. PMID 18337008. doi:10.1016/j.pain.2008.01.024.
[9]
Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain. November 2007, 132 (1-2): 132–41. PMID 17659837. doi:10.1016/j.pain.2007.06.006.
[10]
Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc. Natl. Acad. Sci. U.S.A. January 2007, 104 (2): 660–5. PMC 1752192 . PMID 17194758. doi:10.1073/pnas.0609916104.
[11]
Jhaveri MD, Elmes SJ, Kendall DA, Chapman V. Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats. Eur. J. Neurosci. 2005, 22 (2): 361–70. PMID 16045489. doi:10.1111/j.1460-9568.2005.04227.x.
[12]
Story GM, Cruz-Orengo L. Feel the Burn. American Scientist. 2008, 95 (4): 326–333 [2009-12-03]. ISSN 0003-0996. （原始内容存档于2008-01-19）.
[13]
Gunthorpe MJ, Szallasi A. Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms. Curr. Pharm. Des. 2008, 14 (1): 32–41. PMID 18220816. doi:10.2174/138161208783330754.
[14]
Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL, Bannon AW, Norman MH, Louis JC, Treanor JJ, Gavva NR, Romanovsky AA. Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J. Neurosci. July 2007, 27 (28): 7459–68. PMID 17626206. doi:10.1523/JNEUROSCI.1483-07.2007.
[15]
Gavva NR. Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1. Trends Pharmacol Sci. 2008, 29 (11): 550–557. doi:10.1016/j.tips.2008.08.003.
[16]
Di Marzo V, Starowicz K, Cristino L. TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications. Curr. Pharm. Des. 2008, 14 (1): 42–54. PMID 18220817. doi:10.2174/138161208783330790.
[17]
Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA. TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons. Neuron. 2008, 57 (5): 746–59. PMID 18341994. doi:10.1016/j.neuron.2007.12.027.
[18]
Numazaki, Mitsuko; Tominaga Tomoko; Takeuchi Kumiko; Murayama Namie; Toyooka Hidenori; Tominaga Makoto. Structural determinant of TRPV1 desensitization interacts with calmodulin. Proc. Natl. Acad. Sci. U.S.A. (United States). Jun 2003, 100 (13): 8002–6. ISSN 0027-8424. PMID 12808128. doi:10.1073/pnas.1337252100.
[19]
Morenilla-Palao, Cruz; Planells-Cases Rosa; García-Sanz Nuria; Ferrer-Montiel Antonio. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J. Biol. Chem. (United States). Jun 2004, 279 (24): 25665–72. ISSN 0021-9258. PMID 15066994. doi:10.1074/jbc.M311515200.

深入阅读

Immke DC, Gavva NR. The TRPV1 receptor and nociception. Semin. Cell Dev. Biol. October 2006, 17 (5): 582–91. PMID 17196854. doi:10.1016/j.semcdb.2006.09.004.
Heiner I, Eisfeld J, Lückhoff A. Role and regulation of TRP channels in neutrophil granulocytes.. Cell Calcium. 2004, 33 (5-6): 533–40. PMID 12765698. doi:10.1016/S0143-4160(03)00058-7.
Geppetti P, Trevisani M. Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function.. Br. J. Pharmacol. 2004, 141 (8): 1313–20. PMID 15051629. doi:10.1038/sj.bjp.0705768.
Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.. Pharmacol. Rev. 2006, 57 (4): 427–50. PMID 16382100. doi:10.1124/pr.57.4.6.
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