PURIFICATION AND FUNCTION OF HYPOTHALAMIC PEPTIDES

计划在继续研究中进行几个系列的实验 两种肽，P物质和神经降压素， 在这个实验室中分离和化学定义， 肽，物质K，它是在同一个基因编码， 这些肽具有广泛的但选择性的 分布于整个中枢和外周神经系统 和几种内分泌组织表明这些肽 支持多种生理作用。 拟议的研究 包括：1）阐明神经降压素在中枢神经系统中的作用， LH释放的调节; 2）SP和SK的内分泌调节 垂体前叶和选择性神经元中的基因表达 组织在发育过程中以及分布和功能 垂体前叶中SP的含量; 3）纯化和 SP（和SK）受体的生物化学表征。 进一步 了解P物质和NT在 下丘脑和垂体前叶应该有助于我们 了解这些结构所调控的功能。 了解激素对肽基因调控的影响 开发过程中的表达应该提供重要的见解 神经和激素肽如何对 成熟过程中的内分泌环境。 隔离和化学 SP（和SK）受体的表征将提供一个主要的 进一步了解这些肽调控的过程- 受体相互作用 由于SP（和SK）发挥着重要作用， 例如，在传递疼痛刺激时， 这些肽的活性结合位点的定义可能导致 新的治疗方法的发展。

Several series of experiments are planned in continuing research on two peptides, substance P and neurotensin, that were originally isolated and chemically defined in this laboratory as well as the peptides, substance K, which is coded for in the same gene as substance P. These peptides have widespread but selective distribution throughout the central and peripheral nervous system and several endocrine tissues suggesting that these peptides subserve multiple physiological roles. The proposed studies include: 1) elucidation of the role of neurotensin in the central regulation of LH release; 2) endocrine regulation of SP and SK gene expression in the anterior pituitary and selected neural tissues during development as well as the distribution and function of SP in the anterior pituitary; and, 3) purification and biochemical characterization of SP (and SK) receptors. Further understanding of the physiological role(s) of substance P and NT in the hypothalamus and anterior pituitary should contribute to our understanding of the functions regulated by these structures. Understanding hormonal effects on the regulation of peptide gene expression during development should provide important insights into how neural and hormonal peptides respond to changes in endocrine milieu during maturation. The isolation and chemical characterization of the SP (and SK) receptor will provide a major step towards understanding processes regulated by these peptide- receptor interactions. Since SP (and SK) play important roles, for example, in the transmission of painful stimuli, the chemical definition of the active binding site of these peptides may lead to the development of new therapeutic approaches.