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神经胃肠病学中的 TRP 通道:治疗干预的机会。

TRP channels in neurogastroenterology: opportunities for therapeutic intervention.

机构信息

TARGID - Translational Research Center for Gastrointestinal Disorders, KULeuven, Leuven, Belgium.

出版信息

Br J Pharmacol. 2011 Jan;162(1):18-37. doi: 10.1111/j.1476-5381.2010.01009.x.


DOI:10.1111/j.1476-5381.2010.01009.x
PMID:20804496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3012403/
Abstract

The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.

摘要

瞬时受体电位 (TRP) 阳离子通道超家族的成员参与了众多的细胞功能。在过去的十年中,大量证据表明这些阳离子通道在消化道的不同调节方面起着重要作用。在这篇综述中,我们讨论了 TRP 通道在胃肠道运动、肠神经系统信号传递和内脏感觉调节中的表达模式和作用,并就 TRP 的药理学靶向作为治疗各种胃肠道疾病的策略提供了我们的观点。我们发现,目前关于 TRP 超家族某些成员在神经胃肠病学中的作用的知识相当有限,而其他 TRP 通道的功能,特别是涉及平滑肌细胞收缩(TRPC4、TRPC6)、内脏敏感性和超敏性(TRPV1、TRPV4、TRPA1)的功能则趋于确立。与表达数据相比,关于肠道起搏(TRPC4、TRPC6、TRPM7)、肠神经系统信号传递(TRPCs)和肠内分泌细胞(TRPM5)中 TRP 通道的机制信息则相对缺乏。很明显,几种不同的 TRP 通道在控制胃肠道功能的细胞装置中起着重要作用。它们参与胃肠道运动和吸收、内脏感觉和内脏超敏性的调节。TRP 通道可以被认为是治疗消化疾病、运动障碍和内脏疼痛的有趣靶点。目前,TRPV1 拮抗剂正在开发用于治疗烧心和内脏超敏,但干扰其他 TRP 通道也很有吸引力。然而,它们在胃肠道病理生理学中的作用首先需要进一步阐明。

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本文引用的文献

[1]
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Br J Pharmacol. 2011-11

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Gastroenterology. 2009-12

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