Abstract

Previous studies have shown that metabolic acidosis is associated with enhanced Vmax of Na-H antiporter in brush border membranes of the rabbit kidney. We have recently shown that chronic hypercapnia and post-hypercapnia are also associated with enhanced Vmax of the Na-H antiporter. The mechanism responsible for this increase in Vmax of the Na-H antiporter is unknown. This proposal aims at elucidating the mechanisms responsible for alterations of the Na-H antiporter in acid-base disorders. We will address this issue by studying brush-border membranes from animals with acid-base disorders. To determine the mechanism whereby metabolic or respiratory acidosis increases the Vmax of the Na-H antiporter, we will measure binding of 3H amiloride analogs by brush border membranes. We will also study the Na-H antiporter in primary cultures of the proximal tubule of the rabbit. In this system it is possible to evaluate the role of intracellular pH, glucocorticoids, growth factors and protein synthesis in the adaptive increase in Vmax of the Na-H antiporter in acidosis. In addition, we will study the Na- H antiporter of brush-border membranes and the Na-HCO/3 cotransport in basolateral membranes of animals with acid-base disorders. We postulate that changes in Na-H antiporter are accompanied by parallel changes in NaHCO/3 cotransport. In addition, since glucocorticoids play a role in the adaptive increase in Vmax of Na-H antiporter in acidosis, we postulate that these hormones also influence the Na-HCO/3 cotransport. These studies will shed new light on the mechanisms responsible for the adaptation to acid-base disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036253-06
Application #
3234559
Study Section
General Medicine B Study Section (GMB)
Project Start
1985-01-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Galanter, W L; Ruiz, O S; Labotka, R J et al. (1995) Binding of nitrate to renal brush border membranes studied with 14N nuclear magnetic resonance (NMR). Biochim Biophys Acta 1237:16-22
Kear, F; Ruiz, O S; Arruda, J A (1993) Modulation of renal basolateral Na-phosphate cotransporter by protein kinase A and Ca-dependent protein kinases. Miner Electrolyte Metab 19:373-6
Arruda, J A; Wang, L J; Pahlavan, P et al. (1993) Glucocorticoids and the renal Na-H antiporter: role in respiratory acidosis. Regul Pept 48:329-36
Rubenstein, M; Muchnik, S; Garber, S L et al. (1993) Differential effect of xanthopterin and biopterin on cell growth. Int J Biochem 25:1873-80
Pahlavan, P; Wang, L J; Sack, E et al. (1993) Role of protein kinase C in the adaptive increase in Na-H antiporter in respiratory acidosis. J Am Soc Nephrol 4:1079-86
Pahlavan, P; Mejicano, G; Ruiz, O S et al. (1992) Anion channel in basolateral cortical membranes of the rabbit kidney. Miner Electrolyte Metab 18:386-91
Ruiz, O S; Arruda, J A (1992) ATP-dependent renal H+ translocation: regional localization, kinetic characteristics, and chloride dependence. Proc Soc Exp Biol Med 200:562-70
Ruiz, O S; Arruda, J A (1992) Regulation of the renal Na-HCO3 cotransporter by cAMP and Ca-dependent protein kinases. Am J Physiol 262:F560-5
Kniaz, D; Pahlavan, P; Valaitis, D et al. (1991) High-affinity binding sites for VIP in renal cortical membranes: possible role of VIP in renal transport. Kidney Int 39:266-72
Sack, E M; Arruda, J A (1991) Epidermal growth factor binding to cortical basolateral membranes in compensatory renal hypertrophy. Regul Pept 33:339-48

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