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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK014241-19
Application #
3225210
Study Section
Physiology Study Section (PHY)
Project Start
1976-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
19
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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Maack, T; Okolicany, J; Koh, G Y et al. (1993) Functional properties of atrial natriuretic factor receptors. Semin Nephrol 13:50-60
Price, D A; Okolicany, J; Maack, T (1992) Renal receptors and effects of atrial natriuretic factor in compensatory renal hypertrophy. Kidney Int 42:75-82
Maack, T (1992) Receptors of atrial natriuretic factor. Annu Rev Physiol 54:11-27
Okolicany, J; McEnroe, G A; Koh, G Y et al. (1992) Clearance receptor and neutral endopeptidase-mediated metabolism of atrial natriuretic factor. Am J Physiol 263:F546-53
Koh, G Y; Nussenzveig, D R; Okolicany, J et al. (1992) Dynamics of atrial natriuretic factor-guanylate cyclase receptors and receptor-ligand complexes in cultured glomerular mesangial and renomedullary interstitial cells. J Biol Chem 267:11987-94
Fontoura, B M; Nussenzveig, D R; Timmermans, P B et al. (1991) DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells. Am J Hypertens 4:303S-308S
Okolicany, J; McEnroe, G A; Gregory, L C et al. (1991) Effects of small C-ANF receptor ligands on plasma levels of atrial natriuretic factor, blood pressure, and renal function in the rat. Can J Physiol Pharmacol 69:1561-6
Fontoura, B M; Nussenzveig, D R; Pelton, K M et al. (1990) Atrial natriuretic factor receptors in cultured renomedullary interstitial cells. Am J Physiol 258:C692-9
Nussenzveig, D R; Lewicki, J A; Maack, T (1990) Cellular mechanisms of the clearance function of type C receptors of atrial natriuretic factor. J Biol Chem 265:20952-8

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