NEUROCHEMICAL CONTROL OF OXYTOCIN RELEASE

催产素释放的神经化学控制

• 批准号: 3317903
• 负责人: CLARK GROSVENOR
• 金额: $ 11.47万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317903
• 关键词: dopamine; epinephrine; high performance liquid chromatography; hormone inhibitor; hormone regulation /control mechanism; neuroendocrine system; norepinephrine; opiate alkaloid; oxytocin; radioimmunoassay; scintillation spectrometry; thin layer chromatography; tritium

Suckling initiates a neuroendocrine reflex which releases oxytocin (OT) from the axon terminals of neurons in the supraoptic and paraventricular nuclei (SON/PVN) into the general circulation. Little, however, is known to date about the neurochemical mechanisms involved. The purpose of the proposed investigation is to elucidate the facilitatory and inhibitory neurochemical mechanisms controlling OT secretion in response to suckling in the rat, with emphasis on the roles of catecholamines and opioid peptides both at the level of the CNS and at the level of the neural lobe (NL). Reliance will be placed upon direct analysis of OT concentrations in the plasma using RIA rather than intramammary pressure or milk ejection, which are indirect indices of OT release. Two specific interrelated hypotheses will be tested: 1) Suckling activates central noradrenergic systems that regulate OT release via actions in the SON/PVN and/or in other hypothalamic areas that influence these neurosecretory centers. 2) The release of OT in response to suckling is modulated in the NL a) by dopamine (DA) released from tuberohypophysial axons, b) by endogenous opioid neuropeptides which may serve as transmitters with OT, and c) by circulating norepinephrine (NE) and epinephrine (E) of sympathetic adrenal origin. (Epinephrine is released from the sympathetic-adrenal system into the circulation of the rat in response to suckling.) We will investigate these hypotheses in vivo by determining a) whether suckling affects the turnover of DA, NE, and serotonin (5H-T) in discrete areas of the brain and in the NL; b) whether localized depletions of brain monoamines by the neurotoxins, 6 hydroxydopamine (for NE and DA) and 5, 7 dihydroxytryptamine (for 5H-T), affect the suckling-induced release of OT; c) the effects of centrally and peripherally active monoamine agonists and antagonists and of adrenalectomy upon OT release during suckling; d) the effects of opiate agonists and antagonists and of opioid neuropeptides upon OT release during suckling; and e) whether opiates influence the changes in brain and NL catecholamine turnover induced by suckling. We will also employ in vitro methods (isolated NL and NL synaptosomes) to analyze the effects of monoaminergic and opiate agonists and antagonists upon OT secretion directly at the NL.

哺乳会引发神经内分泌反射，释放催产素 (OT) 来自视上和室旁神经元的轴突末端 原子核（SON/PVN）进入大气循环。 然而，人们知之甚少 迄今为止有关所涉及的神经化学机制的信息。 目的 拟议的研究是为了阐明促进和抑制 控制 OT 分泌以响应哺乳的神经化学机制 在大鼠中，重点关注儿茶酚胺和阿片类药物的作用 CNS 水平和神经叶水平的肽 （荷兰）。 将依赖于对 OT 浓度的直接分析 使用放射免疫分析（RIA）血浆，而不是乳房内压力或乳汁喷射， 这是 OT 释放的间接指数。 两个特定的相互关联的 将测试以下假设：1）哺乳激活中枢去甲肾上腺素能 通过 SON/PVN 和/或其他中的操作来调节 OT 释放的系统 影响这些神经分泌中心的下丘脑区域。 2) 的 哺乳反应中 OT 的释放在 NL a) 中受到多巴胺的调节 (DA) 从结节垂体轴突释放，b) 由内源性阿片类药物释放 可作为 OT 递质的神经肽，以及 c) 交感肾上腺循环去甲肾上腺素（NE）和肾上腺素（E） 起源。 （肾上腺素从交感肾上腺系统释放到 老鼠响应哺乳的循环。）我们将调查 这些假设在体内通过确定 a) 哺乳是否影响 大脑离散区域中 DA、NE 和血清素 (5H-T) 的周转 在荷兰； b) 脑单胺是否因 神经毒素、6-羟基多巴胺（NE 和 DA）和 5、7-二羟基色胺 （对于5H-T），影响哺乳诱导的OT释放； c) 的影响 中枢和外周活性单胺激动剂和拮抗剂 哺乳期间 OT 释放时进行肾上腺切除术； d) 阿片类药物的作用 激动剂和拮抗剂以及阿片类神经肽在 OT 期间释放 乳; e) 阿片类药物是否影响大脑和 NL 的变化 哺乳引起的儿茶酚胺周转。 我们还将采用体外 方法（分离的 NL 和 NL 突触体）来分析 OT 分泌后的单胺能和阿片激动剂和拮抗剂 直接在NL。