TRPV1

瞬態感受器陽離子電壓通道
子分類V，成員1 *[人類]*
瞬態感受器陽離子電壓通道; 子分類V，成員1 [人類]
	TRPV1離子通道同源蛋白四聚體的結構模型，其中每一個單體用青、綠、藍及洋紅色分別標出。其中的4,5-二磷酸基磷脂醯肌醇觸發配體，根據空間填充模型分別用白、紅、橙三種顏色代表碳、氧及磷原子。其周圍的黃色部分為該通道所嵌入其中的雙脂膜的示意情形。
標識
代號	TRPV1; DKFZp434K0220; VR1
擴展標識	遺傳學：602076 鼠基因：1341787 同源基因：12920 IUPHAR: TRPV1 GeneCards: TRPV1 Gene
基因本體論描述
分子功能	· 感受器活動; · 離子通道活動; · 鈣離子通道活動; · 鈣離子結合; · 鈣調蛋白結合; · 陽離子跨膜轉運活動;
細胞成分	· 嵌入質膜; · 膜; · 嵌入膜;
生物過程	· 體溫調節; · 離子轉運; · 鈣離子轉運; · 細胞表面感受器信號轉換; · 化學感受器行為; · 酸鹼度響應; · 熱感響應; · 痛覺感受器; · 溫度感應;
	Sources: Amigo / QuickGO
RNA表達模式
	更多表達數據
直系同源體
物種	人類
Entrez	7442
Ensembl	ENSG00000196689
UniProt	Q8NER1
mRNA序列	NM_018727
蛋白序列	NP_061197
基因位置	Chr 17:; 3.42 – 3.45 Mb
PubMed查詢	[1]
	閱; 論; 編;

TRPV1是指「瞬態感受器電位陽離子通道，子類V，成員1」（transient receptor potential cation channel, subfamily V, member 1），該通道是一個蛋白質，在人類基因中由TRPV1基因所編碼^[2]^[3]。這一通道屬於一種離子通道，是瞬態電壓感受器族中的一員，屬於TRPV組（即瞬態感受器電位陽離子通道，子類V）^[4]。

TRPV1是一個配體門控非選擇性陽離子通道，可以被各種外因性及內因性的物理及化學刺激所激發，例如：溫度超過43 °C、pH值低（酸性環境）、內源性大麻素花生四烯酸乙醇胺、N-花生四烯醯基多巴胺以及辣椒素（辣椒的有效成分）。這一通道被發現存在於中樞神經系統及末梢神經系統上，並且涉及痛覺的傳遞和調製，以及整合各種同疼痛信息^[5]^[6]。

臨床意義

針對多種動物的研究發現，阻止TRPV1發揮作用會導致體溫上升，包括人類及鼠類。這一發現暗示該通道涉及生物體溫調節過程^[7]。而最近，AMG517這種高度針對TRPV1的受體拮抗劑已不再用於臨床試驗，這是因為它會導致體溫升高至無法接受的水平^[8]。近期因類似原因而停用的TRPV1受體拮抗劑還包括GRC 6211以及NGD 8243。另一種化合物SB-705498也被用於類似的臨床試驗，但其對體溫的影響則沒有相關報告^[9]。

TRPV1通道蛋白的後期磷酸化翻譯修飾，對該通道能否發揮正常功能是至關重要的。近期美國衛生教育與福利部下的國家衛生研究所所發表的報告指出，Cdk5促使的磷酸化修飾，對該通道的配體驅動通道開啟的敏感道來說是有重要關係的^[10]。

末梢神經系統

在實驗鼠上的試驗表明，通過使用針對TRPV1的受體拮抗劑，可以明顯減輕炎症反應及神經疼痛的傷害性^[11]。這一結果表明，TRPV1通道是能對辣椒素做出反應的唯一感受器^[12]。

對於人類來說，作用在TRPV1感受器上的藥物，應當能用於治療與多發性硬化症、化療或者截肢有關的神經性疼痛，也能緩解因組織損傷，如骨關節炎導致的炎症有關的疼痛^[13]。

最近幾年，人們才意識到TRPV1通道是體溫調節中的一個環節。這是因為人們發現一些針對TRPV1的選擇性受體拮抗劑會導致體溫升高（高溫症），這說明在體內TRPV1通道通過告知大腦應當降溫，來不間斷的調節著體溫^[7] 。如果因某種原因導致TRPV1通道沒有及時發出這種降溫信號，則體溫會不斷上升。於此類似的，這也是為什麼食用含有辣椒素（針對TRPV1的一種激動劑）的食物會導致流汗——大腦希望通過該方式來降低體溫。最近的一個研究表明，在內臟中TRPV1通道也會持續的工作，通過發出降低體溫的信號來不斷調節體溫^[14]。因此，該通道的主要功能被認為是調節體溫^[15]。

中樞神經系統

TRPV1通道在高級的中樞神經系統中，也有相應的表達。該通道除了被認為可以用於治療神經性疼痛之外，還可以治療其它症狀例如焦慮^[16]。此外，該通道似乎還與海馬區中的長時程抑制效應有關^[17]。而長時程抑制則會減弱形成新的記憶的能力，於此相反的長時程增強效應則會幫助形成記憶。在突觸中形成的抑制與增強模式，則為形成記憶的方式提供了編碼。長時程抑制效應及其導致突觸連結剪枝的效果，對於形成記憶來說是很重要的。針對實驗鼠大腦切片的研究發現，通過熱或者辣椒素的刺激可以引發長時程抑制效應，而辣椒素受體阻斷劑則能阻礙辣椒素所引起的抑制效應^[17]。因此，正如已經在末梢神經系統中應用TRPV1拮抗劑來緩解疼痛那樣，也許將來有可能通過在中樞神經系統中使用這種拮抗劑來治療一些疾病，例如癲癇。

參見

相互作用

TRPV1通道被發現與鈣調節蛋白1^[18]、突觸結合蛋白9（SYT9）^[19]以及N-乙基馬來醯亞胺敏感因子可溶性附著蛋白相關蛋白（SNAPAP）^[19]發生蛋白質-蛋白質相互作用。SNAPAP即SNAP相關蛋白，其中SNAP指可溶性（S）、N-乙基馬來醯亞胺敏感因子（N）、附著蛋白（AP）。

引用

^ 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 （英語）.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^7.0 ^7.1 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Story GM, Cruz-Orengo L. Feel the Burn. American Scientist. 2008, 95 (4): 326–333 [2009-12-03]. ISSN 0003-0996. （原始內容存檔於2008-01-19）.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^17.0 ^17.1 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.
^ 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.
^ ^19.0 ^19.1 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.

深入閱讀

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.

外部連結

醫學主題詞表（MeSH）：Vanilloid+receptors

[pmid17548815-1] 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 （英語）.

[pmid9349813-2] 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.

[pmid11549313-3] 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.

[pmid16382100-4] 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.

[pmid16971522-5] 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.

[pmid12060783-6] 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.

[pmid17392452-7] 7.0 ^7.1 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.

[pmid18337008-8] 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.

[pmid17659837-9] 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.

[pmid17194758-10] 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.

[pmid16045489-11] 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.

[Story_2008-12] Story GM, Cruz-Orengo L. Feel the Burn. American Scientist. 2008, 95 (4): 326–333 [2009-12-03]. ISSN 0003-0996. （原始內容存檔於2008-01-19）.

[pmid18220816-13] 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.

[pmid17626206-14] 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.

[pmid18805596-15] 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.

[pmid18220817-16] 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.

[pmid18341994-17] 17.0 ^17.1 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.

[pmid12808128-18] 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.

[pmid15066994-19] 19.0 ^19.1 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.

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[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]