The role of reduced glutathione in preserving renal function and structure will be investigated, using the isolated perfused rat kidney as a model. We have preliminary evidence that glutathione depletion may produce lesions localized to the thick ascending limb associated with disproportionate reduction in concentrating ability. Specific inhibition of GSH synthesis and cellular depletion of GSH in a variety of ways will be employed, and an attempt made to correlate histological evidence of structural damage to cells and functional alterations, with tissue levels of reduced thiols, using both histochemical and enzymatic methods to evaluate this. The way in which Na-K-ATPase is activated when transepithelial transport is increased will be studied in the isolated perfused elasmobranch rectal gland. Intracellular sodium will be monitored non-invasively and sequentially by a new technique using nuclear magnetic resonance (23Na NMR). Steady-state levels of phosphorus intermediates will also be estimated with 31P NMR, together with the unidirectional rates of phosphate turnover, using the method of saturation transfer. Changes in intracellular electrical potential will be evaluated in separated tubules and cells before and after stimulation of transport, using fluorescent and radioactive probes. Alterations in ouabain binding of rectal gland cells will be assessed before and after secretion is stimulated. The possibility of interchange of pump enzyme between cell interior and plasma membranes by the mechanisms of exocytosis and of membrane internalization will be investigated. The possible role of protein kinase in activating cell membrane Na-K-ATPase will also be explored in direct experiments using partially purified enzyme and protein kinase prepared from rectal gland tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018078-14
Application #
3225926
Study Section
General Medicine B Study Section (GMB)
Project Start
1974-09-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
14
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Prasad, P V; Priatna, A; Spokes, K et al. (2001) Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy. J Magn Reson Imaging 13:744-7
Prasad, P V; Epstein, F H (1999) Changes in renal medullary pO2 during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: effects of aging and cyclooxygenase inhibition. Kidney Int 55:294-8
Priatna, A; Epstein, F H; Spokes, K et al. (1999) Evaluation of changes in intrarenal oxygenation in rats using multiple gradient-recalled echo (mGRE) sequence. J Magn Reson Imaging 9:842-6
Silva, P; Solomon, R J; Epstein, F H (1999) Mode of activation of salt secretion by C-type natriuretic peptide in the shark rectal gland. Am J Physiol 277:R1725-32
Greenfeld, Z; Stillman, I E; Brezis, M et al. (1997) Medullary injury in the ageing rat kidney: functional-morphometric correlations. Eur J Clin Invest 27:346-51
Mulkerrin, E C; Clark, B A; Epstein, F H (1997) Increased salt retention and hypertension from non-steroidal agents in the elderly. QJM 90:411-5
Epstein, F H (1997) Oxygen and renal metabolism. Kidney Int 51:381-5
Gunning, M; Solomon, R J; Epstein, F H et al. (1997) Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland. Am J Physiol 273:R1400-6
Derman, M P; Chen, J Y; Spokes, K C et al. (1996) An 11-amino acid sequence from c-met initiates epithelial chemotaxis via phosphatidylinositol 3-kinase and phospholipase C. J Biol Chem 271:4251-5
Medina, R; Cantley, L; Spokes, K et al. (1996) Effect of water diuresis and water restriction on expression of HSPs-27, -60 and -70 in rat kidney. Kidney Int 50:1191-4

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