PURIFICATION AND FUNCTION OF HYPOTHALAMIC PEPTIDES

在持续的研究中，计划进行几个系列的实验 两种多肽，P物质和神经降压素，最初是 在本实验室中分离和化学定义，以及 多肽，物质K，它在同一个基因中编码，与 这些多肽具有广泛性和选择性。 中枢和外周神经系统的分布 和几个内分泌组织表明这些多肽 服从多种生理角色。建议进行的研究 包括：1)阐明神经降压素在中枢神经系统中的作用 促黄体生成素释放的调节；2)SP和SK的内分泌调节 基因在垂体前叶和精选神经中的表达 发育过程中的组织及其分布和功能 垂体前叶中SP的表达；以及3)纯化和 SP(和SK)受体的生化特性。进一步 对P物质和NT在大鼠脑内的生理作用的认识(S) 下丘脑和垂体前叶应该对我们的 了解这些结构所规定的功能。 了解激素对多肽基因调控的影响 在发育过程中的表达应该提供重要的见解 研究神经肽和荷尔蒙多肽如何对 成熟期的内分泌环境。分离和化学 SP(和SK)受体的特征将提供一个主要的 向了解这些多肽调节的过程迈进一步- 受体相互作用。由于SP(和SK)扮演着重要角色，因此 例如，在痛苦刺激的传递中，化学物质 对这些肽的活性结合部位的定义可能导致 开发新的治疗方法。

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.