BIOLOGY OF COMPENSATORY ADAPTATION IN COLLECTING TUBULE

收集管补偿适应的生物学

• 批准号: 3462996
• 负责人: VESA MATTI VEHASKARI
• 金额: $ 9.07万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462996
• 关键词: acidity /alkalinity; adenylate cyclase; apical membrane; beta adrenergic agent; bicarbonates; cyclic AMP; drug metabolism; epidermal growth factor; homeostasis; hormone regulation /control mechanism; kidney pharmacology; laboratory rabbit; membrane channels; mineralocorticoids; renal tubule; sodium potassium exchanging ATPase; vasopressins

The proposed project examines the signals, nature, and mechanisms of the functional and structural adaptation that occurs in the renal collecting tubule after reduction of renal mass. Since the collecting tubule is the final regulator of urinary excretion of water and solutes, the adaptation of this segment obviously is critical for the maintenance of total body homeostasis. Preliminary studies have shown that intrinsic adaptive changes in the collecting tubule are retained when studied in vitro. Based on preliminary studies, three main hypothesis have been formulated to address the adaptation process: 1) Adaptation of sodium transport and hypertrophy in the cortical collecting tubule (CTT) depend on increased luminal delivery of sodium and/or increased apical sodium permeability, and require the presence of basal mineralocorticoid levels; 2) There is a generalized defect in several cAMP-mediated hormonal actions in the collecting tubule; 3) Growth factors are important in the development of compensatory adaptation; their effect is maintained as altered tubular transport rates. These hypotheses will be tested in vitro in isolated collecting transport rates. These hypotheses will be tested in vitro in isolated collecting tubules from remnant kidneys with several probes including: 1) morphometric studies, 2) biochemical assays (Na-K-ATPase and adenylate cyclase), and 3) functional transport parameters (ion transport, conductivities, intracellular pH measurements). A variety of dietary, in vivo and in vitro pharmacologic, and other maneuvers will be utilized to interfere with the putative mechanisms operative in compensatory adaptation and thus identify the specific role of each. For instance, adaptation in sodium transport will be studied under conditions where each one of the proposed key factors is separately eliminated. Similarly, pharmacologic tools will be used to separately probe several of the steps involved in hormone-cAMP mediated effect in three separate systems (ADH-water permeability in cortical collecting tubule, beta-adrenergic stimulation of bicarbonate secretion in cortical collecting tubule, and cAMP-stimulated bicarbonate absorption in medullary collecting tubule). Effect of growth factors on several cellular functions will also be tested and correlated with the development of compensatory adaptation.

拟议的项目检查了信号，自然和 功能和结构适应的机制 减少肾脏后，发生在肾脏收集小管中 大量的。 由于收集小管是尿的最终调节器 水和溶质的排出，该细分市场的改编 显然对于维持全身至关重要 稳态。 初步研究表明，内在 当收集小管的自适应变化被保留 在体外研究。 基于初步研究，三个主要 已经提出了假设来解决适应 过程：1）适应钠转运和肥大 皮质收集小管（CTT）取决于腔内的增加 递送钠和/或顶端钠渗透率增加， 并需要存在基础盐皮质激素水平； 2） 几种cAMP介导的激素中有广义缺陷 收集小管中的作用； 3）生长因素很重要 在补偿性适应的发展中；他们的效果是 维持为改变的管状运输速率。 这些假设 将在孤立的收集运输速率中在体外测试。 这些假设将在孤立的收集中在体外进行测试 来自残留肾脏的小管，有几个探针，包括：1） 形态计量研究，2）生化测定（NA-K-ATPase和 腺苷酸环化酶）和3）功能转运参数（离子 运输，电导率，细胞内pH测量值）。 一个 饮食，体内和体外药理学以及其他种类 操作将用于干扰推定的 机制在补偿性适应方面运作，从而 确定每个的特定作用。 例如，适应 在每个条件下，将研究钠运输 所提出的关键因素被单独消除。 相似地， 药理学工具将用于单独探测几个 激素训练营介导的效应的步骤三个 单独的系统（皮质收集中的ADH水渗透性 小管，β-肾上腺素能刺激碳酸氢盐分泌 皮质收集小管和营地刺激的碳酸氢盐 髓质收集小管中的吸收）。 增长的影响 几个细胞功能的因素也将被测试，并且 与补偿性适应的发展相关。