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NEUROTRANSMITTER REGULATION OF BETA-ENDORPHIN SECRETION

神经递质对 β-内啡肽分泌的调节

基本信息

批准号：
3449647
负责人：
GREGORY P MUELLER
金额：
$ 2.21万
依托单位：
U.S.UNIFORMED SERVICES UNIV HLTH SCIS
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-03-01 至 1986-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3449647
关键词：
acetylcholine central nervous system dopamine hormone regulation /control mechanism immunologic techniques ion exchange chromatography neural information processing neuroendocrine system neurotransmitters norepinephrine serotonin

项目摘要

The specific aims of this proposal are to determine the roles of brain monoamine and acetylcholine neurotransmitters in regulating the physiologic secretion of pituitary Beta-endorphin 1-31 (B-END1-31) and structurally related peptides in the rat. Two approaches will be used in this investigation. One will involve electrolytic lesion techniques (raphe, locus coeruleus) and the systematic use of pharmacologic agents (receptor agonists and antagonists) to examine the control which brain serotonin, dopamine, norepinephrine and acetylcholine neurons may exert over the basal and stimulated secretion of B-END-like peptides. The drugs to be tested are those which best discriminate between specific functions of receptor subtypes (e.g. serotonin 1 vs serotonin 2; dopamine 1 vs dopamine 2); as necessary these agents will be administered directly into the CNS to limit their actions within the brain. The effects of experimental treatments on plasma levels of total B-END-like immunoreactivity, as well as levels of individual peptides comprising this immunoreactivity will be determined. Specifically, B-END1-31 and B-END1-27, their acetylated forms, and Beta-lipotropin will be isolated from plasma extracts by cation exchange (SP-Sephadex) and high pressure liquid chromatography and subsequently quantified by immunoassay. The second approach in this investigation will correlate the regional turnover of dopamine, norepinephrine and serotonin in the hypothalamus, and dopamine turnover in the pars intermedia, with the physiologic release of B-END-like peptides. These studies will better define the neural mechanism regulating the secretion of B-END-like peptides. Based on the distinctive forms of B-END peptides secreted by the pars distalis and pars intermedia in vitro, chromatographic analysis of B-END-like peptides in plasma may reveal the particular lobe of the pituitary from which B-END-LI is secreted by a given stimulus. Furthermore, these studies may suggest pharmacologic strategies for selectively controlling the secretion of B-END-like peptides in man, approaches which could be useful in the treatment of clinical pain. Ultimately it is hoped that knowledge of the regulation of B-END-like peptides will lead to a greater understanding of the physiologic functions of these hormones and the pituitary gland.

这项建议的具体目的是确定大脑的作用，单胺类和乙酰胆碱类神经递质在生理调节中的作用垂体β-内啡肽1-31（B-END 1 -31）的分泌和结构大鼠体内的相关肽。在此将使用两种方法调查一种将涉及电解损伤技术（中缝，蓝斑）和系统使用药物（受体激动剂和拮抗剂）以检查脑5-羟色胺的对照，多巴胺、去甲肾上腺素和乙酰胆碱能神经元可在基底节上发挥作用，并刺激B-END样肽的分泌。待测药物是那些最能区分受体的特定功能亚型（如血清素1与血清素2;多巴胺1与多巴胺2）;作为必要时，这些药物将直接施用于CNS，以限制它们在大脑中的活动。实验性治疗对总B-END样免疫反应性的血浆水平，以及将测定包含这种免疫反应性的各个肽。具体地，B-END 1 -31和B-END 1 -27，它们的乙酰化形式，和将通过阳离子交换从血浆提取物中分离β-促脂素（SP-Sephadex）和高压液相色谱法，随后通过免疫测定定量。本次调查的第二种方法将将多巴胺、去甲肾上腺素和5-羟色胺在下丘脑，和多巴胺周转中间部，与 B-END样肽的生理释放。这些研究将更好地明确调节B-END样蛋白分泌的神经机制缩氨酸基于B-END肽的独特形式，远侧部和中间部的体外色谱分析血浆中的B-END样肽可能揭示了特定的脑叶， B-END-L1是由给定刺激分泌的垂体。此外，这些研究可能会建议药理学策略，选择性地控制人中B-END样肽的分泌，这些方法可能对临床疼痛的治疗有用。最后，希望对B-END类的调控知识肽将导致更好地了解生理功能，这些激素和脑下垂体。