CELLULAR FUNCTION OF THE JUXTAGLOMERULAR APPARATUS

球旁装置的细胞功能

• 批准号: 2734050
• 负责人: LINDA C. SAMUELSON
• 金额: $ 10.79万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734050
• 关键词: adenosine; arachidonate; eicosanoid metabolism; gene expression; genetically modified animals; glomerular filtration rate; hormone receptor; hormone regulation /control mechanism; in situ hybridization; integrins; juxtaglomerular apparatus; kidney circulation; kidney function; laboratory mouse; nitric oxide synthase; oxytocin; parathyroid hormone related protein; peptidyl dipeptidase A; prostaglandins; protein isoforms; renal tubule; renin angiotensin system

DESCRIPTION (Adapted from the Applicant's Abstract): The juxtaglomerular apparatus (JGA) of the mammalian nephron is a structure which connects the distal tubule with the glomerular vascular pole. It is located at a nephron site where NaCI concentration varies considerably depending upon body salt balance. Previous studies in the applicant's laboratory have established that variations in tubular salt content are sensed, and signals are transmitted to the afferent arteriolar smooth muscle cells and renin-producing granular cells. The result of this information flow is regulation of glomerular vascular tone and renin secretion. The present application combines gene expression studies and functional studies, largely in transgenic animals, in order to clarify the molecular pathways critical for these responses. The first specific aim is to develop and apply methods that are suitable for studying regulation of GFR, blood flow and renin release in the mouse kidney at both the single nephron and organ level, in order to lay the foundation for later studies in genetically modified animals. The second aim is to study the effect of disruption in the regulation of angiotensin and of macula densa-derived nitric oxide on set point and sensitivity of the local vascular regulatory mechanisms, using mice with null mutations in ncNOS and AT1a receptors. The third aim is to evaluate the interactions between adenosine and arachidonic acid metabolities in local regulation in the JGA. The fourth specific aim is to evaluate the role of gene products which show high levels of expression in the JGA, but currently have no recognized regulatory role. Proteins whose possible contribution to JGA function is to be examined are the oxytocin receptor, PTH-related protein, and B6-integrin. The long term goal of these studies is to understand the cellular events responsible for local control of renin secretion and glomerular vascular tone, functions that are of central importance for the control of body fluid volume and arterial blood pressure.

描述（改编自申请人的摘要）：近球状 哺乳动物肾单位（JGA）是连接肾单位的结构 远端肾小管与肾小球血管极。 它位于肾单位 NaCl 浓度随体内盐分变化很大的部位 平衡。 申请人实验室先前的研究已经确定 感测到管状盐含量的变化，并发出信号 传递至传入小动脉平滑肌细胞并 产生肾素的颗粒细胞。 该信息流的结果是 调节肾小球血管张力和肾素分泌。 本申请结合了基因表达研究和功能研究 主要在转基因动物中进行的研究，以阐明分子 对于这些反应至关重要的途径。 第一个具体目标是发展 并应用适合研究 GFR、血液调节的方法 小鼠肾脏中单个肾单位和肾素的流量和肾素释放 器官水平，为后续遗传学研究奠定基础 改造动物。 第二个目标是研究干扰的影响 血管紧张素和致密斑衍生的一氧化氮的调节 局部血管调节机制的设定点和敏感性，使用 ncNOS 和 AT1a 受体无突变的小鼠。 第三个目标是 评估腺苷和花生四烯酸之间的相互作用 JGA 局部调节中的代谢。 第四个具体目标是 评估在中表现出高水平表达的基因产物的作用 JGA，但目前没有公认的监管作用。 蛋白质其 需要检查的是催产素对 JGA 功能的可能贡献 受体、PTH 相关蛋白和 B6 整合素。 这些研究的长期目标是了解细胞事件 负责肾素分泌和肾小球血管的局部控制 音调，对于体液控制至关重要的功能 容量和动脉血压。