ROLE OF NITRIC OXIDE IN INTERSTITIAL CYSTITIS

一氧化氮在间质性膀胱炎中的作用

• 批准号: 6945564
• 负责人: LORI A BIRDER
• 金额: $ 1.49万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6945564
• 关键词: afferent nerve; biological signal transduction; biosensor device; calcium flux; calcium indicator; cats; cell membrane; cellular pathology; chemical structure function; disease /disorder model; electrophysiology; immunocytochemistry; interstitial cystitis; membrane permeability; neuronal transport; neurons; neurotransmitter transport; nitric oxide; tissue /cell culture; urinary bladder epithelium; voltage /patch clamp

DESCRIPTION (Adapted from the Applicant's Abstract): Recent evidence suggests that alterations in afferents or epithelial cells in the urinary bladder can lead to changes in neural excitability and may be part of the etiology of interstitial cystitis (IC). IC is a chronic clinical syndrome of unknown cause and presents with varying and complex sensory symptoms. This may involve a primary defect in afferent neurons or a change in their peripheral environment. Preliminary data indicate that IC in cats can alter the release of chemical mediators (nitric oxide, NO; ATP) from afferent nerves as well as the urothelium. It has been suggested that altered chemical release may influence afferent excitability as well as urothelial membrane function, by increasing the permeability to noxious substances. These data raise the possibility that the urothelium is involved in intercellular signaling in the urinary bladder and neural-epithelial interactions can modulate bladder function. The proposed experiments will use new methods such as cultured urothelial cells and a selective NO porphyrinic microsensor in a naturally occurring animal model of IC (feline interstitial cystitis), which has been demonstrated to have many similarities with IC in humans, to examine the hypothesis that chemical and/or intracellular signaling mechanisms in afferent or epithelial cells in the urinary bladder are altered in IC. Naturally occurring IC rather than acute bladder injury or inflammation models in healthy animals permit more relevant studies of pathophysiology of IC. Aim #1 will evaluation the characteristics of the urothelium in both normal and IC cats. The location of afferent nerves next to the urothelium suggests that urothelial cells might be targets for transmitters released from bladder nerves or that release by epithelial cells could alter the excitability of afferents. Aim #2 will evaluate the characteristics of bladder afferents in both normal and IC cats. We will evaluate the properties of normal bladder afferents to determine how afferents can be altered in IC. These studies may lead to selective pharmacologic interventions aimed at targeting neural-epithelial release or signaling defects and could provide a new prospective on the pathophysiology and clinical management of bladder disorders.

描述（根据申请人的摘要改编）：最近的证据表明 膀胱中的传入或上皮细胞的改变可以 导致神经兴奋性的变化，可能是病因的一部分 间质性膀胱炎（IC）。 IC是未知原因的慢性临床综合症 并出现不同且复杂的感觉症状。这可能涉及 传入神经元的主要缺陷或周围环境的变化。 初步数据表明，猫中的IC可以改变化学物质的释放 传入神经以及 尿铺上皮。有人提出，化学释放的改变可能会影响 通过增加，传入的兴奋性以及尿路上皮膜功能 对有害物质的渗透性。这些数据增加了可能性 尿路上皮参与膀胱中的细胞间信号传导 神经上皮相互作用可以调节膀胱功能。提议 实验将使用新方法，例如培养的尿路上皮细胞和A 在天然发生的动物模型中，选择性无卟啉微传感器 IC（猫的间质性膀胱炎），已证明具有许多 与人类中的IC相似，以研究化学和/或 传入或上皮细胞中的细胞内信号传导机制 膀胱在IC中发生了变化。自然发生的IC而不是急性 健康动物中膀胱损伤或炎症模型允许更相关 IC的病理生理研究。 AIM＃1将评估 正常猫和IC猫的尿路上皮。接下来的神经的位置 对尿路上皮表明尿路上皮细胞可能是 从膀胱神经释放或上皮细胞释放的发射器 可以改变传入的兴奋性。 AIM＃2将评估 正常和IC猫中膀胱传入的特征。我们将 评估正常膀胱传入的特性以确定传入方式 可以在IC中更改。这些研究可能导致选择性药理学 旨在靶向神经上皮释放或信号缺陷的干预措施 并可以为病理生理学和临床提供新的前景 膀胱疾病的管理。