The two major objectives of this proposal are to continue the investigation of the mechanisms underlying the maturation of HCO3- absorption in the juxtamedullary proximal convoluted tubule (JMPCT), and to initiate studies on the embryological origin and development of the acid-base transporting cell, the mitochondria rich (MR) cell, of the collecting duct. Absorption of HCO3- in the isolated perfused rabbit renal JMPCT has been found to surge to adult levels during the fifth and six weeks of postnatal life. This surge was not mediated by a rise in Na-K-ATPase activity, but may be due to an increase in number and activity of Na+-H+ exchangers, and be preceded by an increase in nephron GFR. The studies in this proposal will estimate the number of Na+-H+ exchangers in the luminal membrane by measuring both Na+-dependent H+ effluxes and cell pH during the same postnatal period. The studies in the collecting duct will focus on the function, development, regulation, and origin of the MR cell. In mature isolated perfused cortical and medullary collecting tubules, fluorescent assays will be developed to measure cell pH, probe for the presence of acidic vesicles, mitochondria, endocytosis, exocytosis and carbonic anhydrase, and assess surface binding of lectins. The results of these assays will permit one to distinguish between H+-secreting and HCO3-secreting types of MR cells. Additional studies of the function of the two cell types will assess the effects of ion substitutions on HCO3- transport, measured by microcalorimetry, and on cell pH, measured in individually identified cells with a pH-sensitive fluorescent dye. Because there may be interconversion between the two cell types, the frequency of each will be determined in cortical collecting tubules taken from rabbits subjected to chronic acid-base perturbations. Then the origin of MR cells will be traced back through fetal life to the mesonephric kidney with the same fluorescent methods to establish a fate map. Because the embryonic MR cell may be devoid of most functions that can be probed for with fluorescent dyes, monoclonal antibodies to the surface of the mature differentiated MR cell will be prepared. This antibody should help to identify the MR cell in renal and non-renal embryonic tissues even before differentiated functions appear.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD013232-07
Application #
3312129
Study Section
General Medicine B Study Section (GMB)
Project Start
1979-07-01
Project End
1990-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Matsumoto, T; Fejes-Toth, G; Schwartz, G J (1996) Postnatal differentiation of rabbit collecting duct intercalated cells. Pediatr Res 39:1-12
Brion, L P; Zavilowitz, B J; Suarez, C et al. (1994) Metabolic acidosis stimulates carbonic anhydrase activity in rabbit proximal tubule and medullary collecting duct. Am J Physiol 266:F185-95
Schwartz, G J; Brown, D; Mankus, R et al. (1994) Low pH enhances expression of carbonic anhydrase II by cultured rat inner medullary collecting duct cells. Am J Physiol 266:C508-14
Satlin, L M; Yasoshima, K; Schwartz, G J (1994) H+ secretion in rabbit mesonephric collecting tubule. Am J Physiol 267:F979-86
Matsumoto, T; Winkler, C A; Brion, L P et al. (1994) Expression of acid-base-related proteins in mesonephric kidney of the rabbit. Am J Physiol 267:F987-97
Schwartz, G J; Winkler, C A; Zavilowitz, B J et al. (1993) Carbonic anhydrase II mRNA is induced in rabbit kidney cortex during chronic metabolic acidosis. Am J Physiol 265:F764-72
Matsumoto, T; Fejes-Toth, G; Schweartz, G J (1993) Developmental expression of acid-base-related proteins in the rabbit kidney. Pediatr Nephrol 7:792-7
Schwartz, G J; Zavilowitz, B J; Radice, A D et al. (1992) Maturation of aldose reductase expression in the neonatal rat inner medulla. J Clin Invest 90:1275-83
Schwartz, G J (1992) Does kL/PCr estimate GFR, or does GFR determine k? Pediatr Nephrol 6:512-5
Yasoshima, K; Satlin, L M; Schwartz, G J (1992) Adaptation of rabbit cortical collecting duct to in vitro acid incubation. Am J Physiol 263:F749-56

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