PHYSIOLOGY OF THE PROLACTIN RELEASING PEPTIDES

描述（申请人摘要）：本提案的重点是确定 最近描述的催乳素释放肽（PrRPs）可能发挥的作用 在应激诱导的催乳素分泌升高中（神经内分泌作用， 脑垂体和脑神经调节作用）和自主神经功能 （脑中的神经调节剂作用）。我们假设，在哺乳动物中产生的PrRPs 大脑和脑垂体是正常神经内分泌所必需的， 心血管对压力的反应具体来说，我们假设PrRP， 或在脑下垂体局部产生，或通过 门静脉或外周循环，在分泌 催乳素分泌过多此外，我们假设， 紧张时交感神经张力的升高取决于 脑源性PrRPs和这些肽的去除将损害 动物对压力的心血管反应。我们将解决以下问题 具体目标（问题）：1）身体或预期压力是否会增加 PrRP的循环血浆水平，肽的组织水平（脑， 垂体，肾上腺），或脑中基因的表达（mRNA水平）， 脑下垂体还是肾上腺髓质2)PrRP是否有效释放 多巴胺戒断（发生在压力下）的因素？3)将 PrRP中枢给药刺激催乳素分泌 动物？4)PrRP在大脑中的作用部位是否可以通过 定点注射5)内源性PrRP的受损是否会改变 神经内分泌和心血管对压力的反应描述的研究 本文旨在进一步表征以下药物的药理学和生理学特征： PrRPs已被证明在垂体中起作用， 神经内分泌因子和脑中作为自主神经流出的调节剂。的 最终目标是确定其在维持正常 内分泌和心血管功能，特别是在压力下。这些 研究也将开始检查一个潜在的新的融合内分泌 和对压力的自主反应，从而提供对 多个器官系统对压力的协调反应。

DESCRIPTION (applicant's abstract): The focus of this proposal is to determine the roles the recently described prolactin releasing peptides (PrRPs) may play in stress-induced elevations of prolactin secretion (neuroendocrine actions in pituitary gland and neuromodulatory actions in brain) and autonomic function (neuromodulator actions in brain). We hypothesize that the PrRPs produced in brain and pituitary gland are required for the normal neuroendocrine and cardiovascular responses to stress. Specifically we hypothesize that PrRPs, either produced locally in pituitary gland or delivered to the gland via either the portal or peripheral circulations, play a role in the secretion of prolactin from the gland during stress. Furthermore, we hypothesize that the elevation in sympathetic tone during stress depends upon the actions of brain-derived PrRPs and that removal of those peptides will compromise the animal's cardiovascular response to stress. We will address the following Specific Aims (Questions): 1) Will physical or anticipatory stress elevate circulating plasma levels of PrRP, tissue levels of the peptides (brain, pituitary, adrenal), or expression of the gene (mRNA levels) in brain, pituitary gland or adrenal medulla? 2) Are the PrRPs effective releasing factors in the setting of dopamine withdrawal (which occurs in stress)? 3) Will central administration of PrRP stimulate prolactin secretion in conscious animals? 4) Can the site of action of PrRP in brain be identified by site-specific injections? 5) Will compromise of endogenous PrRP alter the neuroendocrine and cardiovascular responses to stress? The studies described here are designed to further characterize the pharmacology and physiology of the PrRPs, which have been demonstrated to act in the pituitary as neuroendocrine factors and in brain as modulators of autonomic outflow. The ultimate goal is to determine their importance in the maintenance of normal endocrine and cardiovascular function, in particular during stress. These studies will also begin to examine a potentially novel confluence of endocrine and autonomic responses to stress and thereby provide insight into the coordinated responses of multiple organ systems to stress.