CENTRAL CONTROL OF OXYTOCIN SECRETION

催产素是一种下丘脑多肽，在 反射启动乳汁排出，可能还有分娩。它的 分泌似乎是由去甲肾上腺素能中枢控制的 神经起源于脑干，并上升到 下丘脑。某些中枢阿片肽分泌神经 而多巴胺能系统也可能参与控制 催产素释放。可以假设催产素 分泌是由去甲肾上腺素能神经系统控制的。 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 调节催产素分泌的机制，上升 肾上腺素能系统将被药物消融(特定 目标1)和特定的下丘脑生化事件也被研究 在体外作为孤立的区域或使用第三脑室推拉 体内灌流系统。这些实验的一个独特方面是 我们可以同时监测多肽能和儿茶酚胺能 同时进行活动。催产素神经的活动将是 由其在体外释放到介质中或在体内存在而确定 体内的灌流。儿茶酚胺能活动同时存在 通过标记前体的体外生物合成进行监测，或 体内存在特定的胺类代谢物 灌流。这些是分开的，并使用高 高效液相色谱技术。在继续 下丘脑定位及特异性的实验研究 肾上腺素能受体将在体外用 显微解剖的下丘脑区和一种药理学 接近。同时，去甲肾上腺素的重要性 将使用胺来检查自体受体 生物合成/代谢物和体内灌流系统。最后， 阿片肽能(脑啡肽能)和 多巴胺能神经元将使用组合 这些方法。 这项提议的目的是阐明特定的神经元 控制催产素分泌的机制。它是 我觉得这份申请书中提出的研究将产生 不仅关于中央的有价值的新信息 对这种多肽的调节，但它也可能提供一种模型 对于其他神经内分泌和 自主事件。

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.