OPIOIDS AND CENTRAL NEURAL REGULATION OF RENAL FUNCTION

阿片类药物与肾功能的中枢神经调节

• 批准号: 2725131
• 负责人: DANIEL R KAPUSTA
• 金额: $ 8.38万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2725131
• 关键词: antisense nucleic acid; arginine vasopressin; body water; cerebral ventricles; drug administration routes; endogenous opioid; glomerular filtration; hemodynamics; kidney function; laboratory rat; microinjections; neuroendocrine system; neuroregulation; opioid receptor; paraventricular nucleus; potassium; saluresis; urine

Central mu- and kappa-opioid agonists evoke profound changes in urine flow rate and urinary sodium excretion via multiple integrated neural and physiological mechanisms. In addition to these subtypes, a novel opioid-like peptide, nociceptin, and opioid receptor, the ORL1 receptor, have recently been identified. Despite their structural resemblance to endogenous opioid peptides and receptors, the role of nociceptin and the ORL1 receptor in the regulation of renal function, is not known. My short-term goals are to characterize the renal responses produced by activation of the central nociceptin system on renal hemodynamic and excretory function in conscious Sprague-Dawley rats. In addition, the neural and humoral mechanisms, as well as brain sites (e.g. paraventricular nucleus) by which this novel central opioid-like system affects renal function will be investigated. My long-term objectives are to understand the physiological role of the endogenous central nociceptin system in the regulation of renal function and determine how this system interacts with classical opioid systems in this regulatory process. Since to date an antagonist for the ORL1 receptor has not been developed, the role of the endogenous central nociceptin system in the regulation of renal function during basal and stressful environmental conditions will be examined by use of in vivo molecular biology techniques (antisense oligodeoxynucleotide). The funding of an RCDA will help me to accomplish the goals outlined above and to further develop and strengthen my scientific career. In this regard, an RCDA will relieve me from Departmental obligations such as teaching in medical, dental, nursing and allied health courses, and from my substantial duties as Graduate Coordinator for the Department of Pharmacology. I will also be exempt from service on additional committees, both at the Departmental and University level. Together, by securing this award I will be able to devote essentially a full-time effort to my cardiovascular and renal research. The Department of Pharmacology and LSU Medical center provide a supportive environment for the development of my research career. Service is available from the LSUMC Biotechnology Unit for the synthesis of the antisense oligodeoxynucleotides. Facilities are also available within the University for computer and statistical consultation. There also exists a number of other basic research and clinical scientists that maintain active research programs in cardiovascular and renal physiology. The fact that Department faculty receive considerable support from federal granting agencies means that expertise and equipment is readily available. In summary, an RCDA will greatly enhance my research productivity and scientific career.

中央Mu-和Kappa-Apoid激动剂引起了尿液的深刻变化 通过多个集成神经的流量和尿钠排泄 和生理机制。 除了这些亚型， 阿片类肽，诺耐蛋白和阿片受体ORL1受体，ORL1受体， 最近已经确定了。 尽管结构上的相似之处 内源性阿片类肽和受体，Nocceptin和the的作用 肾功能调节中的ORL1受体尚不清楚。我的 短期目标是表征由 在肾脏血流动力学和 有意识的sprague-dawley老鼠中的排泄功能。 另外， 神经和体液机制以及大脑部位（例如 副脑核）这种新型的中央阿片类药物样系统 影响肾功能将被研究。 我的长期目标 要了解内源中心的生理作用 肾功能调节中的NociTptin系统，并确定如何 该系统在此调节中与经典阿片类药物系统进行交互 过程。 由于迄今为止，ORL1受体的拮抗剂尚未 开发的是内源性中央诺环蛋白系统在 调节基础和压力环境期间肾功能 将通过使用体内分子生物学来检查疾病 技术（反义寡脱氧核苷酸）。 RCDA的资金将帮助我实现概述的目标 在上面并进一步发展和加强我的科学生涯。 在 在这方面，RCDA可以减轻我的部门义务 作为医学，牙科，护理和联盟健康课程的教学，以及 从我担任部门研究生协调员的大量职责 药理学。 我还将免除其他服务 委员会，分校和大学一级。 一起， 通过获得该奖项，我将能够从本质上专职 为我的心血管和肾脏研究而努力。 药理学系和LSU医疗中心提供 支持我的研究职业的支持环境。 可从LSUMC生物技术单元获得合成的服务 反义寡脱氧核苷酸的。 设施也可用 在大学内进行计算机和统计咨询。 那里 还有许多其他基础研究和临床科学家 维持心血管和肾脏中的积极研究计划 生理。 部门教师获得了相当大的事实 联邦授予机构的支持意味着专业知识和 设备很容易获得。总而言之，RCDA将大大增强 我的研究生产力和科学生涯。