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一氧化氮与稳态控制:一种有助于自主神经和神经内分泌整合的细胞间信号分子?

Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration?

作者信息

Stern Javier E

机构信息

Department of Pharmacology and Toxicology, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.

出版信息

Prog Biophys Mol Biol. 2004 Feb-Apr;84(2-3):197-215. doi: 10.1016/j.pbiomolbio.2003.11.015.

DOI:10.1016/j.pbiomolbio.2003.11.015
PMID:14769436
Abstract

Accumulated evidence indicates that nitric oxide (NO) plays a pivotal role in the central control of bodily homeostasis, including cardiovascular and fluid balance regulation. Two major neuronal substrates mediating NO actions in the control of homeostasis are the paraventricular nucleus (PVN) of the hypothalamus, considered a key center for the integration of neuroendocrine and autonomic functions, and the supraoptic nucleus (SON). In this work, a comprehensive review of NO modulatory actions within the SON/PVN, including NO actions on neuroendocrine and autonomic outputs, as well as the cellular mechanisms underlying these effects is provided. Furthermore, this review comprises recent progress from our laboratory that adds to our current understanding of the cellular sources, targets and mechanisms underlying NO actions within neuroendocrine and autonomic hypothalamic neuronal circuits. By combining in vitro patch clamp recordings, tract-tracing neuroanatomy, immunohistochemistry and live imaging techniques, we started to shed light into the cellular sources and signals driving NO production within the SON and PVN, as well as NO actions and mechanisms targeting discrete neuronal populations within these circuits. Based on this new information, we have expanded one of the current working models in the field, highlighting a key role for NO as a signaling molecule that facilitates crosstalk among various cell types and systems. We propose that this dynamic NO signaling mechanisms may constitute a neuroanatomical and functional substrate underlying the ability of the SON and PVN to coordinate complex neuroendocrine and autonomic output patterns.

摘要

越来越多的证据表明,一氧化氮(NO)在机体稳态的中枢控制中起着关键作用,包括心血管和体液平衡调节。在稳态控制中,介导NO作用的两个主要神经元底物是下丘脑室旁核(PVN),它被认为是神经内分泌和自主功能整合的关键中心,以及视上核(SON)。在这项工作中,我们对SON/PVN内的NO调节作用进行了全面综述,包括NO对神经内分泌和自主输出的作用,以及这些作用的细胞机制。此外,本综述还包括我们实验室的最新进展,这些进展加深了我们目前对神经内分泌和自主下丘脑神经元回路中NO作用的细胞来源、靶点和机制的理解。通过结合体外膜片钳记录、神经束追踪神经解剖学、免疫组织化学和实时成像技术,我们开始阐明驱动SON和PVN内NO产生的细胞来源和信号,以及针对这些回路中离散神经元群体的NO作用和机制。基于这些新信息,我们扩展了该领域目前的一个工作模型,强调了NO作为一种信号分子在促进各种细胞类型和系统之间串扰方面的关键作用。我们提出,这种动态的NO信号机制可能构成SON和PVN协调复杂神经内分泌和自主输出模式能力的神经解剖学和功能基础。

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