RENAL TRANSPORT AND METABOLISM OF PROTEINS

蛋白质的肾脏运输和代谢

• 批准号: 3150904
• 负责人: THOMAS M MAACK
• 金额: $ 19.42万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3150904
• 关键词: autoradiography; glomerular filtration; hydrolysis; insulin; isolation perfusion; kidney metabolism; lysozyme; macromolecule; nephrosis; pancreatic ribonuclease; parathyroid hormones; peptide hormone; pinocytosis; proteinuria; radiotracer; renal failure; renal tubular transport; renin; somatotropin

The proposed research is aimed at acquiring information on the quantitative aspects and mechanisms of tubular absorption and renal metabolism of proteins and peptide hormones. The isolated perfused rat kidney will be used to determine: a) the concentration of low molecular weight proteins in the glomerular filtrate and hence filtered loads andtubular absorption rates, b) the kinetics of tubular absorption, including its capacity, affinity, specificity, selectivity and effect of inhibitors and c) the kinetics of intracellular hydrolysis of absorbed proteins and the nature of th resulting metabolites. A non-filtering isolated perfused rat kidney model will be used to study peritubular metabolism of pepetide hormones, particularly that of parathyroid hormone (PTH). In this study, attempts will be made to determine: a) the kinetics of interaction of PTH with its receptors at the peritubular side and b) the approximate molecular weights, antigenicity and biological activity of metabolites originating from the peritubular hy drolysis of PTH. Using the isolated perfused proximal convoluted tubule of the rabbit, we will study the kinetics and mechanisms of tubular absorption of albumin with the aim of determining: a) the tubular absorption maximum (TM) of albumin, b) the influence of contact time, fluid reabsorption, and inhibitors of metabolism and endocytosis on tubular absorption of albumin, and c) the influence of net charge of albumin on its tubular absorption rates. In all of these studies a new metod of labelling proteins with tritium to very high specific activity without changes in structure, antigenicity and biological activity of the molecules will be used. Hopefully, the results will elucidate the role of the kidney in the turnover, regulation of plasma levels, and metabolic transformations of proteins and peptide hormones and the mechanisms involved. In addition, the information acquired may provide new insights into the pathophysiology of proteinurias and contribute to the understanding of hormonal imbalances in renal failure.

拟议的研究旨在获取定量信息， 肾小管吸收和肾代谢的方面和机制 蛋白质和肽激素。 将离体灌注的大鼠肾脏 用于测定：a）低分子量蛋白质的浓度 在肾小球滤液中，因此过滤的负荷和肾小管吸收 率，B）肾小管吸收的动力学，包括其容量， 抑制剂的亲和力、特异性、选择性和效果，以及c） 吸收蛋白质的细胞内水解动力学和 从而产生代谢物。 大鼠离体肾脏非滤过性灌流 模型将用于研究肽类激素的管周代谢， 特别是甲状旁腺激素（PTH）。 在这项研究中，尝试 将进行测定：a）PTH与其 管周侧的受体和B）近似分子量， 代谢产物的抗原性和生物活性 PTH小管周围水解。 使用离体灌注的近端 本实验旨在研究其动力学和机制 肾小管吸收白蛋白的目的是确定：a） 白蛋白的肾小管吸收最大值（TM），B）接触的影响 时间，液体重吸收，代谢和内吞抑制剂， 肾小管吸收白蛋白，和c）净电荷的影响， 白蛋白对其肾小管吸收率的影响。 在所有这些研究中， 用氚标记蛋白质以获得极高比活度的方法 而不改变结构、抗原性和生物活性， 分子将被使用。 希望这些结果能阐明 肾在周转，调节血浆水平，代谢 蛋白质和肽类激素的转化及其机制 涉案 此外，获得的信息可能会提供新的见解 蛋白尿的病理生理学，并有助于 肾功能衰竭的症状有哪些