PLASTICITY AT SYNAPSES IN THE LOWER URINARY TRACT

下尿路突触的可塑性

• 批准号: 2900265
• 负责人: GEORGE T SOMOGYI
• 金额: $ 16.56万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900265
• 关键词: G protein; acetylcholine; alpha adrenergic receptor; biological signal transduction; calcium channel; calcium flux; electrostimulus; enzyme mechanism; high performance liquid chromatography; human subject; human tissue; laboratory rat; muscarinic receptor; neural facilitation; neural plasticity; neurons; neurophysiology; neurotransmitter transport; norepinephrine; phosphoprotein phosphatase; protein kinase; protein kinase C; receptor expression; synapses; tissue /cell culture; urinary bladder

DESCRIPTION (Adapted from the Applicant's Abstract): The prejunctional modulatory receptors can be new targets for pharmacological manipulation of lower urinary tract and also possible sites for pathologically-induced changes that can lead to a disruption of normal voiding function. The experiments in this proposal will evaluate two major questions. The first deals with the intracellular mechanisms (e.g., signal transduction pathways) underlying presynaptic muscarinic and adrenergic facilitation of transmitter release in the urinary bladder of rats and human. We will investigate: (1) the contribution of extracellular calcium entry via different voltage gated calcium channels to presynaptic facilitation, (2) the role of tonic G protein inhibition of calcium channels, (3) the function of intracellularly released calcium with special attention to calcium-induced calcium release, (4) the role of protein kinases and phosphatases. We will extend the investigations to the neurons of the major pelvic ganglion where both the transmitter release and the direct response of calcium channels to the facilitatory processes can be studied. The second major topic deals with the influence of pathology on presynaptic modulation. Changes in presynaptic modulation may occur in hyperactive bladders induced by spinal cord injury, by bladder hyperactivity induced by inflammation, and by aging. It is expected that the proposed experiments will provide new insights into the pathophysiologic mechanisms underlying neurogenic disorders of the bladder and may lead to new pharmacological approaches for the treatment of these disorders.

描述（改编自申请人的摘要）： 调节受体可能是药理学操纵的新目标 降低尿路，也可能用于病理诱导的位点 可能导致正常空隙函数破坏的变化。 这 该提案中的实验将评估两个主要问题。 第一个 处理细胞内机制（例如，信号转导途径） 发射器的潜在突触前毒蕈碱和肾上腺素能促进 在大鼠和人类的膀胱中释放。 我们将调查：（1） 细胞外钙进入通过不同电压门的贡献 突触前促进的钙通道，（2）补品G的作用 钙通道的蛋白质抑制，（3）细胞内的功能 释放钙，特别注意钙诱导的钙释放， （4）蛋白激酶和磷酸酶的作用。 我们将扩展 对主要骨盆神经节神经元的调查 发射机释放和钙通道对 可以研究促进过程。 第二个主要主题涉及 病理对突触前调节的影响。 变更 突触前调节可能发生在由脊柱诱导的多动膀胱中 绳索损伤，通过炎症和衰老引起的膀胱多动症。 预计拟议的实验将为您提供新的见解 神经源性疾病的病理生理机制 膀胱并可能导致新的药理学方法来治疗 这些疾病。