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CENTRAL CONTROL OF OXYTOCIN SECRETION

催产素分泌的中央控制

基本信息

批准号：
3409560
负责人：
DAVID K SUNDBERG
金额：
$ 11.47万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-04-01 至 1991-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3409560
关键词：
adrenergic receptor brain stem catecholamines chromatography enkephalins hypothalamus interneurons laboratory rat neural information processing neuroendocrine system neuropeptide receptor neuropharmacology oxytocin perfusion radioassay sympathetic nervous system tissue /cell culture

项目摘要

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。反射性的催乳和可能的分娩。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