RENAL TRANSPORT AND METABOLISM OF PROTEINS

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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.