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5-羟色胺的代谢动力学与功能性胃肠病的研究靶点

Metabolic kinetics of 5-hydroxytryptamine and the research targets of functional gastrointestinal disorders.

作者信息

Jing Fuchun, Zhang Jun

机构信息

Department of Gastroenterology, Second Hospital Affiliated to the Medical School, Xi'an Jiaotong University, No. 157, West Road 5, Xi'an City, 710004, Shaanxi Province, China,

出版信息

Dig Dis Sci. 2014 Nov;59(11):2642-8. doi: 10.1007/s10620-014-3244-x. Epub 2014 Jun 12.

Abstract

5-Hydroxytryptamine (5-HT) is an important neurotransmitter in both the central and enteric nervous systems. It has diverse functions in regulating gastrointestinal motility and visceral sensitivity, emotion, appetite, pain and sensory perception, cognition, sexual activity and sleep. These functions are mainly associated with the metabolic kinetics of 5-HT in different tissues. Tryptophan hydroxylase is the rate-limiting enzyme and modulates serotonin synthesis. Vesicular monoamine transporter 1 plays a role in 5-HT storage and release. Degradation of 5-HT is mediated by monoamine oxidase-A. All these factors influence the action of 5-HT in vivo. Functional gastrointestinal disorders (FGIDs) are characterized by a series of symptoms including abdominal pain, diarrhea, constipation, anxiety and depression, in the absence of identifiable structural or biochemical abnormalities. They are frequently accompanied by changed gut motility or visceral sensitivity. An increasing body of research has found FGIDs to be closely associated with 5-HT, and drugs such as citalopram, paroxetine, venlafaxine, alosetron, tegaserod, prucalopride and mosapride have all been developed or discovered from the perspective of the metabolic kinetics of 5-HT. This review discusses the relationship between the metabolic kinetics of 5-HT and research targets in the field of FGIDs and suggests areas of future study that may be useful for understanding these disorders and identification of potential therapeutic targets.

摘要

5-羟色胺(5-HT)是中枢神经系统和肠神经系统中的一种重要神经递质。它在调节胃肠动力、内脏敏感性、情绪、食欲、疼痛与感觉知觉、认知、性活动及睡眠等方面具有多种功能。这些功能主要与5-HT在不同组织中的代谢动力学相关。色氨酸羟化酶是限速酶,可调节血清素的合成。囊泡单胺转运体1在5-HT的储存和释放中发挥作用。5-HT的降解由单胺氧化酶A介导。所有这些因素都会影响5-HT在体内的作用。功能性胃肠病(FGIDs)的特征是出现一系列症状,包括腹痛、腹泻、便秘、焦虑和抑郁,且不存在可识别的结构或生化异常。它们常伴有肠道动力改变或内脏敏感性变化。越来越多的研究发现FGIDs与5-HT密切相关,西酞普兰、帕罗西汀、文拉法辛、阿洛司琼、替加色罗、普芦卡必利和莫沙必利等药物均是从5-HT代谢动力学的角度研发或发现的。本综述讨论了5-HT代谢动力学与FGIDs领域研究靶点之间的关系,并提出了未来可能有助于理解这些疾病及确定潜在治疗靶点的研究方向。

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