The long term goal of our research is to define the mechanisms by which the proximal tubule of the mammalian kidney transports sodium, bicarbonate, chloride and water and to characterize the manner by which they are physiologically regulated. To achieve this goal multiple techniques (free-flow micropuncture, in situ microperfusion, in vitro microperfusion, isolated membrane vesicles) are used and the data obtained by these various means are evaluated for internal consistency and integrated into a physiologically meaningful framework.
Specific aims are: 1) To further characterize the nature of the sodium-dependent and sodium-independent components of acidification. 2) To examine the role of adaptive changes in Na/H antiporter activity in modulating the rate of acidification. 3) To examine the role of sodium-dependent and sodium-independent mechanisms in the regulation of cell pH. 4) To determine the response of cell pH to changes in luminal and peritubular bicarbonate, Pco2 and pH. 5) To examine the role of cell pH in the regulation of the rate of acidification in response to changes in acid-base and potassium balance, and the administration of various agents such as glucocorticoids or parathormone. 6) To further characterize the luminal and basolateral mechanisms for transcellular Na and Cl transport. 7) To obtain more precise estimates of the transepithelial driving forces for water movement in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM027045-06
Application #
3151705
Study Section
General Medicine B Study Section (GMB)
Project Start
1980-06-01
Project End
1990-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Preisig, P A; Rector Jr, F C (1988) Role of Na+-H+ antiport in rat proximal tubule NaCl absorption. Am J Physiol 255:F461-5
Alpern, R J (1987) Apical membrane chloride/base exchange in the rat proximal convoluted tubule. J Clin Invest 79:1026-30
Preisig, P A; Ives, H E; Cragoe Jr, E J et al. (1987) Role of the Na+/H+ antiporter in rat proximal tubule bicarbonate absorption. J Clin Invest 80:970-8
Daniel, T O; Ives, H E (1987) Cyclosporin A inhibits kinase C-independent activation of the Na+/H+ exchanger by PDGF and vanadate. Biochem Biophys Res Commun 145:111-7
Ives, H E; Daniel, T O (1987) Interrelationship between growth factor-induced pH changes and intracellular Ca2+. Proc Natl Acad Sci U S A 84:1950-4
Alpern, R J; Chambers, M (1987) Basolateral membrane Cl/HCO3 exchange in the rat proximal convoluted tubule. Na-dependent and -independent modes. J Gen Physiol 89:581-98
Verkman, A S; Alpern, R J (1987) Kinetic transport model for cellular regulation of pH and solute concentration in the renal proximal tubule. Biophys J 51:533-46
Cogan, M G; Huang, C L; Liu, F Y et al. (1986) Effect of atrial natriuretic factor on acid-base homeostasis. J Hypertens Suppl 4:S31-4
Ives, H E; Chen, P Y; Verkman, A S (1986) Mechanism of coupling between Cl- and OH- transport in renal brush-border membranes. Biochim Biophys Acta 863:91-100
Cogan, M G (1986) Atrial natriuretic factor can increase renal solute excretion primarily by raising glomerular filtration. Am J Physiol 250:F710-4

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