Serotonin receptor signaling and regulation via β-arrestins.
Serotonin receptor signaling and regulation via β-arrestins.
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DOI：
10.3109/10409238.2010.516741
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发表时间：
2010-12
影响因子：
6.5
通讯作者：
Schmid CL
中科院分区：
文献类型：
--
作者：
Bohn LM;Schmid CL
5-羟色胺受体是15个不同基因的产物，其中14个是G蛋白偶联受体。这些受体在广泛的细胞类型中表达，包括不同的神经元群体，并促进多器官系统中不同的功能反应。这些受体对于调节它们的同源神经递质5-羟色胺和内源性色胺的体内效应是重要的。此外，许多药物的作用直接或间接地通过5-羟色胺受体介导，包括抗抑郁药、抗精神病药物、抗焦虑药、助眠药、偏头痛疗法、胃肠疗法和致幻药物。越来越明显的是，5-羟色胺受体可以参与由配体的化学性质决定的差异信号，并且表现出倾向于诱导特定信号级联的配体被认为具有“功能选择性”。阐明细胞信号通路介导对5-羟色胺和其他激动剂的生理反应是一个活跃的研究领域，并将成为一个前瞻性的焦点，以确定如何有效和选择性地促进有益的5-羟色胺能拟态，同时避免有害的临床副作用。本文重点介绍了β-arrestins对5-羟色胺2A、2C和四种受体的调节作用，这可能是体内偏向受体反应的一个支点。
Serotonin receptors are the product of 15 distinct genes, 14 of which are G protein-coupled receptors. These receptors are expressed in a wide range of cell types, including distinct neuronal populations, and promote diverse functional responses in multiple organ systems. These receptors are important for mediating the in vivo effects of their cognate neurotransmitter, serotonin, as well as the endogenous tryptamines. In addition, the actions of many drugs are mediated, either directly or indirectly, through serotonin receptors, including antidepressants, antipsychotics, anxiolytics, sleep aids, migraine therapies, gastrointestinal therapeutics and hallucinogenic drugs. It is becoming increasingly evident that serotonin receptors can engage in differential signaling that is determined by the chemical nature of the ligand and that ligands that demonstrate a predilection for inducing a particular signaling cascade are considered to have “functional selectivity”. The elucidation of the cellular signaling pathways that mediate the physiological responses to serotonin and other agonists is an active area of investigation and will be an onward-looking focal point for determining how to effectively and selectively promote beneficial serotonergic mimicry while avoiding unwanted clinical side effects. This review highlights the modulation of serotonin 2A, 2C, and four receptors by β-arrestins, which may represent a fulcrum for biasing receptor responsiveness in vivo.