The long-term objectives of this application are to elucidate the mechanisms and regulation of renal tubular calcium transport.
The specific aim i s to investigate the role of cytosolic free calcium in parathyroid hormone-mediated and -independent calcium reabsorption in the cortical thick ascending limb of Henle's loop and in the connecting tubule, which are two important calcium-reabsorbing segments of the nephron. Young growing rabbits will be fed a calcium-replete or -deficient diet. Individual cortical thick ascending limbs and connecting tubules will be dissected from their kidneys and perfused in vitro. Epithelial calcium transport will be measured with calcium-45 or by continuous-flow microcolorimetry. Cytosolic free calcium concentration will be measured simultaneously in the same perfused tubule segment by quantitative fluorescence microscopy using fura-2 as an intracellular calcium indicator. Perfusion and bathing solution compositions will be manipulated independently and in concert to identify potential plasma membrane calcium transport processes at both the luminal and anti-luminal sides of the cell. The individual effects of luminal and peritubular extracellular fluid calcium concentration on cytosolic free calcium concentration will be assessed, and the role of cytosolic free Ca, whether as a second messenger in response to parathyroid hormone or as part of a transcellular Ca flux, will be determined. The regulation of urinary calcium excretion is important to calcium homeostasis. For example, all mammalian species that have been studied, including the rabbit, markedly reduce calcium excretion when fed a calcium-deficient diet. Although parathyroid homone probably is an important factor in augmenting calcium reasbsorption under these conditions, the mechanisms by which it acts and the nature of parathyroid hormone-independent mechanisms underlying renal tubular conservation of calcium are unknown. The propose studies will provide new information that will advance our knowledge in this area from the epithelial to the cellular level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035985-04
Application #
3234300
Study Section
General Medicine B Study Section (GMB)
Project Start
1985-01-01
Project End
1990-08-31
Budget Start
1989-08-01
Budget End
1990-08-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Michael Reese Hospital
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60616
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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