Ma Sherie, Smith Craig M, Blasiak Anna, Gundlach Andrew L
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia.
Br J Pharmacol. 2017 May;174(10):1034-1048. doi: 10.1111/bph.13659. Epub 2016 Dec 4.
Relaxin-3 is a member of a superfamily of structurally-related peptides that includes relaxin and insulin-like peptide hormones. Soon after the discovery of the relaxin-3 gene, relaxin-3 was identified as an abundant neuropeptide in brain with a distinctive topographical distribution within a small number of GABAergic neuron populations that is well conserved across species. Relaxin-3 is thought to exert its biological actions through a single class-A GPCR - relaxin-family peptide receptor 3 (RXFP3). Class-A comprises GPCRs for relaxin-3 and insulin-like peptide-5 and other peptides such as orexin and the monoamine transmitters. The RXFP3 receptor is selectively activated by relaxin-3, whereas insulin-like peptide-5 is the cognate ligand for the related RXFP4 receptor. Anatomical and pharmacological evidence obtained over the last decade supports a function of relaxin-3/RXFP3 systems in modulating responses to stress, anxiety-related and motivated behaviours, circadian rhythms, and learning and memory. Electrophysiological studies have identified the ability of RXFP3 agonists to directly hyperpolarise thalamic neurons in vitro, but there are no reports of direct cell signalling effects in vivo. This article provides an overview of earlier studies and highlights more recent research that implicates relaxin-3/RXFP3 neural network signalling in the integration of arousal, motivation, emotion and related cognition, and that has begun to identify the associated neural substrates and mechanisms. Future research directions to better elucidate the connectivity and function of different relaxin-3 neuron populations and their RXFP3-positive target neurons in major experimental species and humans are also identified.
This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.
松弛素-3是结构相关肽超家族的成员，该超家族包括松弛素和胰岛素样肽激素。在松弛素-3基因被发现后不久，松弛素-3就被鉴定为大脑中一种丰富的神经肽，在少数γ-氨基丁酸能神经元群体中具有独特的拓扑分布，且在物种间高度保守。人们认为松弛素-3通过单一的A类G蛋白偶联受体——松弛素家族肽受体3（RXFP3）发挥其生物学作用。A类包括松弛素-3、胰岛素样肽-5以及其他肽（如食欲素和单胺递质）的G蛋白偶联受体。RXFP3受体被松弛素-3选择性激活，而胰岛素样肽-5是相关RXFP4受体的同源配体。过去十年获得的解剖学和药理学证据支持松弛素-3/RXFP3系统在调节对应激、焦虑相关行为和动机行为、昼夜节律以及学习和记忆的反应中发挥作用。电生理学研究已经确定RXFP3激动剂在体外能直接使丘脑神经元超极化，但尚无体内直接细胞信号转导效应的报道。本文概述了早期研究，并重点介绍了最近的研究，这些研究表明松弛素-3/RXFP3神经网络信号在唤醒、动机、情绪和相关认知的整合中发挥作用，并且已经开始确定相关的神经底物和机制。还确定了未来的研究方向，以更好地阐明主要实验物种和人类中不同松弛素-3神经元群体及其RXFP3阳性靶神经元的连接性和功能。
本文是关于松弛素家族肽及其受体理解的最新进展主题部分的一部分。要查看本部分的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc。
