NITRIC OXIDE IN BLADDER NEURAL EPITHELIAL SIGNALING

描述(改编自申请人的摘要)：近期证据 提示神经递质一氧化氮(NO)可能参与了 下尿路的各种功能和一些 排尿障碍。初步数据表明，NO可以被释放 通过各种刺激从尿路上皮和传入神经发出 增加了尿路上皮参与细胞间的可能性 膀胱里的信号。有人建议说，改变 NO水平可能影响传入兴奋性和尿路上皮 膜功能。控制因素和控制机制的阐明 膀胱中的急性和/或慢性NO释放可能提供 对膀胱功能障碍病理的基本见解。这个 拟议的实验将使用新的方法，如培养尿路上皮 细胞和选择性的一氧化氮微传感器来检测其作用 NO在膀胱神经-上皮相互作用中的作用。目标#1将 评估尿路上皮细胞是否可能参与细胞间 化学信号或通讯，以及神经是否可能调节 信号因子从上皮细胞释放出来。的位置 尿路上皮旁的传入神经提示尿路上皮细胞 可能是膀胱神经释放的神经递质的目标。目标2 将确定改变NO浓度是否通过以下方式改变膀胱功能 影响膀胱神经的特性和/或扰乱 尿路上皮屏障。我们将评估NO对上皮细胞的影响 功能(跨上皮阻力或通透性的变化) 除了使用c-fos(作为传入活动的监控器)来确定 传入神经参与NO对膀胱功能的影响。 目标3将评估病理对神经上皮细胞的影响 下尿路的相互作用和NO释放。改建 一氧化氮水平可能影响膀胱感觉神经的兴奋性 也会对上皮细胞产生不利影响，增加对 可能导致膜屏障丧失的有毒物质 与某些疾病相关的正直。因此，有选择性地 旨在改变NO水平的药物干预可以提供 对膀胱的认识和临床处理的新途径 精神错乱。

DESCRIPTION (Adapted from the Applicant's Abstract): Recent evidence suggests the neurotransmitter nitric oxide (NO) may be involved in a variety of functions in the lower urinary tract and in a number of voiding disorders. Preliminary data indicate that NO can be released from the urothelium as well as afferent nerves by various stimuli raising the possibility that the urothelium is involved in intercellular signaling in the urinary bladder. It has been suggested that alterations in NO levels may influence afferent excitability as well as urothelial membrane function. Elucidation of factors and mechanisms controlling acute and/or chronic NO release in the urinary bladder may provide fundamental insights into the pathology of bladder dysfunction. The proposed experiments will use new methods such as cultured urothelial cells and a selective NO porphyrinic microsensor to examine the role of NO in neural-epithelial interactions in the urinary bladder. Aim #1 will evaluate whether urothelial cells may be involved in intercellular chemical signaling or communication and also whether nerve may regulate the signaling factors released from the epithelium. The location of afferent nerves next to the urothelium suggests that urothelial cells might be targets for transmitters released from bladder nerves. Aim #2 will determine if altered NO concentration alters bladder function by affecting the properties of bladder nerves and/or disrupting the urothelial barrier. We will evaluate the effect of NO on epithelial function (changes in transepithelial resistance or permeability) in addition to using c-fos (as a monitor of afferent activity) to determine the involvement of afferents in the effect of NO on bladder function. Aim 3 will evaluate effect of pathology on neural-epithelial interactions and NO release from the lower urinary tract. Alterations in NO levels may affect excitability of sensory nerves in the bladder as well as adversely affect the epithelium, increasing permeability to toxic substances that may contribute to loss of membrane barrier integrity associated with certain diseases. Thus, selective pharmacologic interventions aimed at altering NO levels could provide a new approach to our understanding and clinical management of bladder disorders.