BIOLOGY OF COMPENSATORY ADAPTATION IN COLLECTING TUBULE

拟议的项目检查信号、性质和 功能和结构适应机制 肾功能减退后发生于肾集合管 质量。 由于集合管是尿液的最终调节器 水和溶质的排泄，该部分的适应 显然对于维持全身至关重要 体内平衡。 初步研究表明，内在 集合管的适应性变化在以下情况下被保留： 体外研究。 根据初步研究，主要有以下三点： 提出假设来解决适应问题 过程：1）钠转运和肥大的适应 皮质集合管 (CTT) 依赖于管腔的增加 钠的输送和/或心尖钠渗透性的增加， 并需要存在基础盐皮质激素水平； 2） 几种 cAMP 介导的激素存在普遍缺陷 在集合管中的作用； 3）生长因子很重要 补偿性适应的发展；他们的效果是 维持改变的管状运输速率。 这些假设 将在体外测试分离收集转运率。 这些假设将在单独收集的体外进行测试 使用多个探针从残肾中提取肾小管，包括：1) 形态测量研究，2) 生化测定（Na-K-ATP酶和 腺苷酸环化酶），和3）功能运输参数（离子 运输、电导率、细胞内 pH 测量）。 一个 各种饮食、体内和体外药理学等 将利用演习来干扰假定的 机制在补偿性适应中起作用，因此 确定每个人的具体角色。 例如，适应 钠转运将在每个人的条件下进行研究 所提出的关键因素被单独消除。 同样， 药理学工具将用于分别探测几个 涉及激素-cAMP 介导的三个作用的步骤 独立系统（ADH-皮质收集中的水渗透性 肾小管，β-肾上腺素能刺激碳酸氢盐分泌 皮质集合管和 cAMP 刺激的碳酸氢盐 髓质集合管的吸收）。 生长效果 还将测试影响多种细胞功能的因素 与补偿性适应的发展相关。

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.