BIOLOGY OF COMPENSATORY ADAPTATION IN COLLECTING TUBULE

拟议的项目检查信号、性质和 功能和结构适应的机制 发生在肾减容后的肾集合管 质量。由于集合管是尿液的最终调节器 水和溶质的排泄，这一部分的适应 显然对整个身体的维持是至关重要的 动态平衡。初步研究表明，内在的 在以下情况下，收集小管的适应性变化被保留 在体外研究。根据初步研究，主要有三个方面 已经提出了假说来解决这种适应问题 过程：1)钠转运和肥大的适应 皮质集合管(CTT)依赖于管腔增大 钠的输送和/或心尖钠渗透性的增加， 并要求存在基础盐皮质激素水平；2) 有几种cAMP介导的激素普遍存在缺陷。 在集合管中的作用；3)生长因子是重要的 在代偿性适应的发展中；它们的影响是 维持为改变的小管转运速率。这些假设 将在体外进行隔离收集传输速率的测试。 这些假说将在体外进行隔离采集试验。 用几种探头从残肾取小管：1) 形态计量学研究，2)生化分析(Na-K-ATPase和 腺苷环化酶)，以及3)功能转运参数(离子 传输、电导率、细胞内pH测量)。一个 各种饮食，体内和体外药理，以及其他 演习将被用来干扰假定的 补偿适应的运作机制，因此 确定每个角色的具体角色。例如，改编自 钠的传输将在以下条件下进行研究 提议的关键因素中的一部分被单独删除。同样， 药理学工具将被用来分别探索几个 激素-cAMP介导效应的三个步骤 分离系统(ADH-皮质收集中的水渗透性 肾小管β-肾上腺素能刺激小鼠碳酸氢盐分泌 皮质集合管和cAMP刺激的碳酸氢盐 髓集合管吸收)。增长的影响 还将测试几种细胞功能的因素，并 与代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.