Abstract

The long-term objectives of this application are to elucidate the mechanisms and regulation of renal tubular calcium transport.
The specific aims of this proposal are to investigate the plasmalemmal transport mechanisms regulating cytosolic free calcium concentration and epithelial calcium absorption in cells of the rabbit connecting tubule and cortical thick ascending limb of Henle's loop, which are important calcium-reabsorbing segments of the nephron. Rabbits will be sacrificed and individual connecting tubules and cortical thick ascending limbs will be dissected from their kidneys and perfused in vitro. Cytosolic free concentrations of calcium, sodium, and hydrogen ions will be measured in segments (photon-counting photometry) and individual cells (photon-counting photometry and digital video - imaging) by quantitative fluorescence microscopy. The compositions of both luminal perfusion and peritubular bathing solutions will be manipulated independently and in concert to identify plasmalemmal calcium transport processes at both the luminal and basolateral sides of the cell. In addition to the roles of sodium and hydrogen ions, the actions of parathyroid hormone, the main calcium-regulating hormone in the kidney, will be studied. The regulation of urinary calcium excretion is important to calcium homeostasis. Hypercalciuria, a major determinant of renal stone disease, is the primary disorder of urinary calcium excretion in humans. The proposed studies will provide new information on the cellular and plasmalemmal handling of calcium within the nephron that will advance our knowledge in this area from the epithelial to the cell membrane level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK035985-06
Application #
3234298
Study Section
General Medicine B Study Section (GMB)
Project Start
1985-01-01
Project End
1995-06-30
Budget Start
1991-08-15
Budget End
1992-06-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Oklahoma Health Sciences Center
Department
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117

  Publications

Liu, L; Khastgir, A; McCauley, J M et al. (1996) RT-PCR microlocalization of mRNAs for calbindin D28k and vitamin D receptor in the murine nephron. Am J Physiol 270:F677-81
Lau, K; Bourdeau, J E (1995) Parathyroid hormone action in calcium transport in the distal nephron. Curr Opin Nephrol Hypertens 4:55-63
Chong, S S; Kozak, C A; Liu, L et al. (1995) Cloning, genetic mapping, and expression analysis of a mouse renal sodium-dependent phosphate cotransporter. Am J Physiol 268:F1038-45
Liu, L; Ng, M; Iacopino, A M et al. (1994) Vitamin D receptor gene expression in mammalian kidney. J Am Soc Nephrol 5:1251-8
Bourdeau, J E (1993) Mechanisms and regulation of calcium transport in the nephron. Semin Nephrol 13:191-201
Liu, L; Dunn, S T; Christakos, S et al. (1993) Calbindin-D28k gene expression in the developing mouse kidney. Kidney Int 44:322-30
Bourdeau, J E; Taylor, A N; Iacopino, A M (1993) Immunocytochemical localization of sodium-calcium exchanger in canine nephron. J Am Soc Nephrol 4:105-10
Barr, D R; Sadowski, D L; Hu, J et al. (1991) Characterization of the renal and intestinal adaptations to dietary calcium deprivation in growing female rabbits. Miner Electrolyte Metab 17:32-40
Hou, S H; Zhao, J; Ellman, C F et al. (1991) Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate. Am J Kidney Dis 18:217-24
Bourdeau, J E; Eby, B K (1990) cAMP-stimulated rise of [Ca2+]i in rabbit connecting tubules: role of peritubular Ca. Am J Physiol 258:F751-5

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