BIOLOGY OF COMPENSATORY ADAPTATION IN COLLECTING TUBULE

拟议的项目审查的信号，性质， 功能和结构适应机制， 发生在肾集合小管减少后，肾 马萨诸塞州 由于集合小管是尿液的最终调节器， 水和溶质的排泄，这部分的适应 显然对维持整个身体至关重要 体内平衡 初步研究表明， 在收集小管中的适应性变化被保留， 在体外研究。 根据初步研究， 假设已经制定了解决适应 过程：1）钠转运和肥大的适应， 皮质集合管（CTT）依赖于管腔面积的增加 钠的递送和/或增加的顶端钠渗透性， 并需要基础盐皮质激素水平的存在; 2） 有一个普遍的缺陷，在几个cAMP介导的激素 在集合小管中的作用; 3）生长因子是重要的 在补偿性适应的发展中;它们的作用是 维持改变的肾小管转运速率。 这些假设 将在离体条件下测试收集转运率。 这些假设将在离体收集中进行测试 用几种探针从残余肾脏中提取小管，包括：1） 形态测定研究，2）生化测定（Na-K-ATP酶和 腺苷酸环化酶），和3）功能性转运参数（离子 运输、电导率、细胞内pH测量）。 一 各种饮食，体内和体外药理学，以及其他 机动将被用来干扰假定的 补偿性适应机制， 确定每个人的具体角色。 例如，适应 钠转运将在每一个 提出的关键因素分别消除。 同样地， 药理学工具将被用来分别探测几个 三种激素-cAMP介导的作用所涉及的步骤 分离系统（ADH-皮层收集中的水渗透性 肾小管，β-肾上腺素能刺激碳酸氢盐分泌， 皮质集合小管和cAMP刺激的碳酸氢盐 髓质集合小管吸收）。 菌作用 还将测试几种细胞功能的因素， 与代偿性适应的发展有关。

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.