Bladder Regulation by Corticotropin-Releasing Factor

促肾上腺皮质激素释放因子对膀胱的调节

• 批准号: 7140376
• 负责人: RITA VALENTINO
• 金额: $ 24.31万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140376
• 关键词: corticotropin releasing factor; electrophysiology; gene deletion mutation; genetically modified animals; hormone receptor; hormone regulation /control mechanism; laboratory mouse; laboratory rat; messenger RNA; neurons; neuroregulation; polymerase chain reaction; receptor expression; spinal cord; urinary bladder; urinary tract obstruction; urination

DESCRIPTION (provided by applicant): This is an application for an Exploratory/Developmental Project in response to PA-03-136,"Basic Research in the Bladder and Lower Urinary Tract". Harrington's nucleus, a pentane nucleus with descending projections to lumbosacral preganglionic neurons, regulates parasympathetic outflow to the bladder. Bladder distention activates Barrington's nucleus, which then coordinates visceral (contraction) and central (arousal) responses to the stimulus. Corticotropin-releasing factor (CRF) is a prominent neurotransmitter in Barrington's nucleus neurons and is therefore poised to modulate urinary function. Moreover, pharmacological manipulation of CRF may provide a novel treatment of urinary dysfunctions. In spite of its prominence in the pontine micturition circuit, the role of CRF in micturition and the impact of manipulating CRF on urodynamic function remain unexplored. This proposal will determine the role of CRF in the pontine-spinal circuit (AIM 1) and whether manipulation of CRF in the spinal cord can improve urodynamic function that has been compromised by partial obstruction (AIM 2). Additionally, the impact of partial obstruction on components of the pontine micturition pathway will be identified (AIM 3). Cystometry will be used to quantify effects of selective activation or antagonism of CRF receptors in the spinal cord on urodynamics in unanesthetized rats with unobstructed or partially obstructed bladder. Conversely, the impact of bladder obstruction on single unit activity of Barrington's nucleus neurons, CRF mRNA expression in Barrington's nucleus neurons and CRF- receptor mRNA expression in the spinal cord will be quantified. These studies unite complementary expertise from laboratories in urology and basic neuroscience to increase our knowledge of the central regulation of urinary function in normal and pathological state.

描述（由申请人提供）：这是响应PA-03-136的探索/发展项目的应用程序，“膀胱中的基础研究和较低的尿路”。哈灵顿的核是一种戊烷核，对腰椎前神经神经元的降次投影可调节副交感神经流向膀胱。膀胱扩张激活了Barrington的核，然后将内脏（收缩）和中央（唤醒）对刺激的反应进行协调。皮质激素释放因子（CRF）是Barrington核神经元中突出的神经递质，因此有望调节尿功能。此外，CRF的药理学操纵可能会提供新的尿功能障碍治疗。尽管它在庞蒂汀排尿电路中具有突出性，但CRF在排尿中的作用以及操纵CRF对尿动力功能的影响仍未得到探索。该建议将确定CRF在桥刺脊柱回路中的作用（AIM 1）以及脊髓中CRF的操纵是否可以改善因部分阻塞而损害的尿动力功能（AIM 2）。另外，将确定部分阻塞对桥丁尿素途径组成部分的影响（AIM 3）。囊肿将用于量化脊髓中CRF受体的选择性激活或拮抗脊髓中CRF受体的拮抗作用对静脉注射大鼠的尿动力学的影响，该尿动力学有未扰动或部分阻塞的膀胱。相反，将量化膀胱阻塞对Barrington核神经元单位活性，Barrington核神经元中的CRF mRNA表达以及脊髓中CRF受体mRNA表达的影响。这些研究将泌尿外科实验室和基本神经科学实验室的互补专业知识统一，以增加我们对正常和病理状态下泌尿功能的中心调节的了解。