TRP 通道在消化系统中的作用。

TRP channels in the digestive system.

机构信息

Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitátsplatz 4, A-8010 Graz, Austria.

出版信息

Curr Pharm Biotechnol. 2011 Jan 1;12(1):24-34. doi: 10.2174/138920111793937862.

Abstract

Several of the 28 mammalian transient receptor potential (TRP) channel subunits are expressed throughout the alimentary canal where they play important roles in taste, chemo- and mechanosensation, thermoregulation, pain and hyperalgesia, mucosal function and homeostasis, control of motility by neurons, interstitial cells of Cajal and muscle cells, and vascular function. While the implications of some TRP channels, notably TRPA1, TRPC4, TRPM5, TRPM6, TRPM7, TRPV1, TRPV4, and TRPV6, have been investigated in much detail, the understanding of other TRP channels in their relevance to digestive function lags behind. The polymodal chemo- and mechanosensory function of TRPA1, TRPM5, TRPV1 and TRPV4 is particularly relevant to the alimentary canal whose digestive and absorptive function depends on the surveillance and integration of many chemical and physical stimuli. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 appear to be essential for the absorption of Ca(2+) and Mg(2+), respectively, while TRPM7 appears to contribute to the pacemaker activity of the interstitial cells of Cajal, and TRPC4 transduces smooth muscle contraction evoked by muscarinic acetylcholine receptor activation. The implication of some TRP channels in pathological processes has raised enormous interest in exploiting them as a therapeutic target. This is particularly true for TRPV1, TRPV4 and TRPA1, which may be targeted for the treatment of several conditions of chronic abdominal pain. Consequently, blockers of these TRP channels have been developed, and their clinical usefulness has yet to be established.

摘要

28 种哺乳动物瞬时受体电位 (TRP) 通道亚基中的几种在整个消化道中表达,在味觉、化学和机械感觉、体温调节、疼痛和痛觉过敏、黏膜功能和稳态、神经元、Cajal 间质细胞和肌肉细胞控制运动以及血管功能中发挥重要作用。虽然一些 TRP 通道,特别是 TRPA1、TRPC4、TRPM5、TRPM6、TRPM7、TRPV1、TRPV4 和 TRPV6 的作用已经得到了详细的研究,但其他 TRP 通道在消化功能方面的作用理解还远远落后。TRPA1、TRPM5、TRPV1 和 TRPV4 的多模态化学和机械感觉功能与消化道特别相关,其消化和吸收功能取决于对许多化学和物理刺激的监测和整合。TRPV5 和 TRPV6 以及 TRPM6 和 TRPM7 似乎分别对 Ca(2+)和 Mg(2+)的吸收是必不可少的,而 TRPM7 似乎有助于 Cajal 间质细胞的起搏活动,TRPC4 则介导由毒蕈碱乙酰胆碱受体激活引起的平滑肌收缩。一些 TRP 通道在病理过程中的作用引起了人们极大的兴趣,将它们作为治疗靶点加以利用。这在 TRPV1、TRPV4 和 TRPA1 尤其如此,它们可能成为治疗几种慢性腹痛的靶点。因此,已经开发了这些 TRP 通道的抑制剂,但其临床用途尚未确定。

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