The proposal will test the hypothesis that membrane conductance is regulated through the mediation of intracellular messengers, and that this regulation secondarily affects both the cell membrane potential and electrogenic membrane transport processes. Specifically, this application will assess the role of the adenylate cyclase/cAMP mediated messenger pathway and the inositol phospholipid messenger pathway in regulating membrane conductances and membrane transport in brush border and basolateral membrane vesicles of rat renal proximal tubule. Additionally, this proposal will determine whether hormonally induced changes in these messenger pathways result in changes in permeability, ionic conductances and transport in isolated convoluted and straight segments of proximal tubules, and in membrane vesicles derived from these heterogeneous nephron sites. To accomplish these goals, membrane permeabilities and conductances will be evaluated with the fluorescent and isotopic assays that have been developed in this laboratory, and transport will be examined utilizing specific substrates that are electrogenically transported in either the brush border or basolateral membranes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK001856-05
Application #
3080693
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1988-08-01
Project End
1993-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Medow, M S; Lipkowitz, M S (1994) Developmental changes of renal brushborder membrane ionic permeability. Biochim Biophys Acta 1191:219-24
London, R D; Berson, L; Lipkowitz, M S (1993) Hormonal modulation of ionic permeability in human red blood cells. J Am Soc Nephrol 3:1607-12
Lipkowitz, M S; London, R D; Beck, J C et al. (1992) Hormonal regulation of rat renal proximal tubule brush-border membrane ionic permeability. Am J Physiol 263:F144-51
London, R D; Lipkowitz, M S; Abramson, R G (1992) Altered membrane ionic permeability in a rat model of chronic renal failure. Kidney Int 42:300-7
Beck, J C; Lipkowitz, M S; Abramson, R G (1991) Ontogeny of Na/H antiporter activity in rabbit renal brush border membrane vesicles. J Clin Invest 87:2067-76
London, R D; Lipkowitz, M S; Sinert, R H et al. (1989) Modulation of ionic permeability in a nonpolarized cell: effect of cAMP. Am J Physiol 257:F985-93
Lipkowitz, M S; Abramson, R G (1989) Modulation of the ionic permeability of renal cortical brush-border membranes by cAMP. Am J Physiol 257:F769-76