TRANSPORT PROCESSES OF URINARY ACIDIFICATION

尿液酸化的转运过程

• 批准号: 3483572
• 负责人: PHILIP R STEINMETZ
• 金额: $ 20.68万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483572
• 关键词: acetazolamide; acidosis; active transport; adenosinetriphosphatase; aldosterone; anions; apical membrane; bicarbonates; body fluid osmolarity; carbon dioxide; carbonate dehydratase; cell membrane; chlorine; cyclic AMP; cytoskeleton; hormone regulation /control mechanism; hormones; hydrogen transport; ion transport; membrane permeability; parathyroid hormones; passive transport; pinocytosis; urinalysis; urinary bladder; urinary bladder epithelium; urine acidity

The overall organization of urinary acidification has been defined by a variety of studies of the intact kidney and individual nephrons in vivo, yet relatively little is known about the transport processes across the individual cell membranes--their biochemical nature, their rate-limiting factors, and their organization within the epithelial cell layer. The proposed research extends our work on the control of the rate of urinary acidification in the turtle urinary bladder and focuses on the nature of the transport processes across the cell membranes, i.e. the proton pump at the luminal membrane and the efflux of bicarbonate across the serosal membrane. The proton pump characteristics will be analyzed according to a kinetic model consisting of two components: a catalytic unit responsible for active H+ translocation and a membrane channel with a finite resistance to H+ flow. This model simulates the observed relationship between transport rate (JH) and Delta MuH in the linear region and will be tested in the nonlinear regions at large and small Delta MuH. In addition to kinetic factors, JH is regulated by the number of H+ pumps present in the luminal membrane of the carbonic anhydrase(CA) containing cell population. The role of endocytosis and exocytosis will be examined by morphometric techniques during CO2 stimulation of JH with and without agents inhibiting cytoskeletal function. In a combined biochemical and morphologic approach to the isolation of the H+ pumps, we will test the hypothesis that a distinctive rod-shaped intramembrane particle that occurs in abundance in the luminal and vesicular membranes of the CA cells contains components of the H+-translocating ATPase. Freeze fracture studies of membrane fractions will be correlated with the activity of oligomycin- and ouabain-resistant ATPase. In related efforts, we will examine two HC03- transport systems which depend on C1- and occur in the same epithelium, one in series with the H+ pump and one parallel to the H+ pump. The possibility will be explored that the parallel HCO3- secretory system occurs in a subpopulation of CA cells and is composed of the same transport elements in a different arrangement across the two cell membranes. These studies should advance the understanding of the cellular mechanisms of urinary acidification and provide new insights into epithelial acid-base transport in general.

尿酸化的总体组织结构由以下定义： 对完整肾脏和单个肾单位的各种体内研究， 然而，人们对跨越太平洋的运输过程知之甚少。 单个细胞膜--它们的生物化学性质，它们的限速作用 因子及其在上皮细胞层内的组织。 的 拟议的研究扩展了我们在控制尿流率方面的工作， 酸化在海龟膀胱和重点的性质， 穿过细胞膜的运输过程，即质子泵， 管腔膜和碳酸氢盐穿过浆膜的流出 膜的 质子泵的特性将根据一个 动力学模型由两部分组成：一个催化单元负责 对于活性H+转运和具有有限阻力的膜通道， H+流量 该模型模拟了观察到的 传输速率（JH）和Δ MuH在线性区域，并将进行测试 在大和小Δ MuH的非线性区域中。 除了 动力学因素，JH是调节的H+泵的数量存在于 含碳酸酐酶（CA）细胞群的腔膜。 内吞作用和胞吐作用的作用将通过形态计量学方法进行检查。 在有和没有抑制剂的情况下，在JH的CO2吞吐期间的技术 细胞骨架功能 从生物化学和形态学的角度 到H+泵的隔离，我们将测试假设， 一种独特的杆状膜内颗粒，大量存在于 CA细胞的腔膜和囊膜含有以下成分： H+-转运ATP酶。 膜组分的冷冻断裂研究 将与寡霉素和哇巴因耐药的活性相关 ATP酶 在相关的工作中，我们将研究两个HC 03运输系统， 其依赖于C1-，并且发生在同一上皮中，一个与另一个串联， 一个与H+泵并联。 可能性是 探索了平行的HCO 3-分泌系统发生在亚群中， CA细胞，并由相同的运输元件组成，在不同的 在两个细胞膜上的排列。 这些研究应该向前推进 了解尿酸化的细胞机制， 提供了新的见解上皮酸碱转运一般。