CENTRAL CONTROL OF OXYTOCIN SECRETION

催产素分泌的中央控制

• 批准号: 3409555
• 负责人: DAVID K SUNDBERG
• 金额: $ 12.39万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3409555
• 关键词: brain stem; catecholamines; chromatography; hypothalamus; interneurons; neural information processing; neuroendocrine system; neuropharmacology; oxytocin; perfusion; radioassay; sympathetic nervous system; tissue /cell culture

Oxytocin is a hypothalamic peptide which is important in the reflex initiation of milk ejection and perhaps partuition. Its secretion appears to be centrally controlled by noradrenergic nerves originating in the brain stem and ascending to the hypothalamus. Certain central opiate peptide secreting nerves and a dopaminergic system may also be involved in the control of oxytocin release. The hypothesis can be made that oxytocin secretion is controlled by the ascending noradrenergic tract by mechanisms that resemble descending noradrenergic control of cardiovascular function. In order, to examine the neural mechanisms regulating oxytocin secretion, the ascending adrenergic systems will be pharmacologically ablated (specific aim 1) and certain biochemical hypothalamic events studied either as isolated areas in vitro or using a third ventricular push-pull perfusion system in vivo. A unique aspect of these experiments is that we can monitor both peptidergic and catecholaminergic activity simultaneously. Activity of the oxytocin nerve will be determined by its release into the media in vitro or its presence in the in vivo perfusate. Catecholaminergic activity is concurrently monitored by its in vitro biosynthesis from a labeled precursor, or by the presence of specific amine metabolites in the in vivo perfusate. These are separated and measured using a high performance liquid chromatographic technique. In continuing experiments the hypothalamic location and specificity of adrenergic receptors will be determined in vitro using microdissected hypothalamic areas and a pharmacological approach. Simultaneously the importants of noradrenergic autoreceptors will be examined using the amine biosynthesis/metabolites and in vivo perfusion systems. Finally, the involvement of opiate peptidergic (enkephalinergic) and dopaminergic neurons will be examined using a combination of these approaches. The intent of this proposal is to elucidate the specific neuronal mechanisms responsible for control of oxytocin secretion. It is felt that the studies proposed in this application will yield valuable new information regarding not only the central regulation of this peptide, but also that it might provide a model for the central mechanisms of other neuroendocrine and autonomic events.

催产素是一种下丘脑肽，其在哺乳动物中是重要的。 反射性启动排奶，也许还有排奶。 其 分泌似乎是由去甲肾上腺素能神经递质 起源于脑干并上升到 下丘脑 某些中枢阿片肽分泌神经 多巴胺能系统也可能参与控制 催产素释放 假设催产素 分泌由去甲肾上腺素能上行束控制， 类似于去甲肾上腺素能下行控制的机制， 心血管功能 为了检查神经系统 调节催产素分泌的机制， 肾上腺素能系统将被阻断（特异性 目的1）和某些生化下丘脑事件的研究， 作为体外隔离区域或使用第三心室推拉 体内灌注系统。 这些实验的一个独特之处在于 我们可以同时监测肽能和儿茶酚胺能 活动同时。 催产素神经的活动将 通过其在体外释放到培养基中或其在 体内灌注液。 儿茶酚胺能活性同时 通过其从标记前体的体外生物合成来监测，或 通过在体内存在特定的胺代谢物 灌注液 这些是分开的，并使用高 高效液相色谱技术 在继续 实验下丘脑的位置和特异性， 肾上腺素能受体将在体外使用 显微解剖的下丘脑区域和药理学 approach. 同时，去甲肾上腺素能神经元 将使用胺检查自身受体 生物合成/代谢物和体内灌注系统。 最后， 阿片肽能（脑啡肽能）和 多巴胺能神经元将使用以下组合进行检查： 这些方法。 这个建议的目的是阐明特定的神经元 负责控制催产素分泌的机制。 是 我认为，本申请中提出的研究将产生 有价值的新信息不仅涉及中央 调节这种肽，而且它可能提供一个模型 其他神经内分泌和 自主神经事件