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尿路中的瞬时受体电位香草酸亚型1(TRPV1,香草酸受体):表达、功能及临床应用

TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications.

作者信息

Avelino António, Cruz Francisco

机构信息

Institute of Histology and Embryology, Faculty of Medicine of Porto, Alameda Hernani Monteiro, 4200-319 Porto, Portugal.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2006 Jul;373(4):287-99. doi: 10.1007/s00210-006-0073-2. Epub 2006 May 24.

Abstract

The transient receptor potential vanilloid subfamily 1 (TRPV1) is an ion channel activated by capsaicin, heat, protons and endogenous ligands such as anandamide. It is largely expressed in the urinary tract of mammals. Structures in which the receptor expression is firmly established include sensory fibers and urothelial cells, although the presence of TRPV1 in other cell types has been reported. As in other systems, pain perception was the first role attributed to TRPV1 in the urinary tract. However, it is now increasingly clear that TRPV1 also regulates the frequency of bladder reflex contractions, either through direct excitation of sensory fibers or through urothelial-sensory fiber cross talk involving the release of neuromediators from the epithelial cells. In addition, the recent identification of the receptor in urothelial and prostatic cancer cells raise the exciting hypothesis that TRPV1 is involved in cell differentiation. Desensitization of the receptor by capsaicin and resiniferatoxin has been investigated for therapeutic purposes. For the moment, lower urinary tract dysfunctions in which some benefit was obtained include painful bladder syndrome and overactive bladder of neurogenic and non-neurogenic origin. However, desensitization may become obsolete when non-toxic, potent TRPV1 antagonists become available.

摘要

瞬时受体电位香草酸亚家族1(TRPV1)是一种离子通道,可被辣椒素、热、质子以及内源性配体(如花生四烯乙醇胺)激活。它在哺乳动物的泌尿系统中大量表达。虽然已有报道称TRPV1存在于其他细胞类型中,但受体表达已得到确证的结构包括感觉纤维和尿路上皮细胞。与其他系统一样,疼痛感知是TRPV1在泌尿系统中最初被赋予的作用。然而,现在越来越清楚的是,TRPV1还通过直接刺激感觉纤维或通过涉及上皮细胞释放神经介质的尿路上皮-感觉纤维相互作用来调节膀胱反射收缩的频率。此外,最近在尿路上皮癌细胞和前列腺癌细胞中发现了该受体,这提出了一个令人兴奋的假说,即TRPV1参与细胞分化。为了治疗目的,已经研究了辣椒素和树脂毒素对该受体的脱敏作用。目前,已取得一定益处的下尿路功能障碍包括疼痛性膀胱综合征以及神经源性和非神经源性起源的膀胱过度活动症。然而,当无毒、强效的TRPV1拮抗剂问世时,脱敏作用可能会过时。

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