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NMR studies of phosphate metabolism in the isolated perfused kidney of developing rats
M Barac-Nieto1, R K Gupta, A Spitzer
1Albert Einstein College of Medicine, Department of Pediatrics, Bronx, NY 10461.
Insights
Growing kidneys exhibit lower intracellular phosphate (Pi) levels, prompting adaptive changes in Pi transport. This study reveals how intracellular Pi directly regulates renal Pi reabsorption during development.
Area of Science:
- Nephrology
- Cell Physiology
- Biochemistry
Background:
- Renal phosphate (Pi) reabsorption capacity changes with Pi demand during growth.
- These changes suggest intracellular Pi directly regulates renal Pi transport.
- A low intracellular Pi concentration ([Pi]i) in developing kidneys may drive adaptive transport changes.
Purpose of the Study:
- To investigate the hypothesis that low intracellular Pi concentration in developing kidneys leads to adaptive changes in renal Pi transport.
- To measure intracellular Pi and phospho-metabolite concentrations and Pi turnover rates in growing and adult rat kidneys.
Main Methods:
- Utilized 31P-nuclear magnetic resonance (NMR) spectroscopy.
- Measured intracellular concentrations of NMR-visible Pi, phospho-metabolites (ATP, ADP), and Pi turnover rates.
- Compared isolated perfused kidneys from 3-4 week old (growing) and 12-13 week old (adult) rats.
Main Results:
- Kidneys of growing rats had significantly lower intracellular Pi (1.7 mM) compared to adult rats (2.7 mM).
- ATP and ADP concentrations were similar between age groups, indicating a high phosphorylation potential in younger kidneys.
- Pi turnover rates, assessed by ATP synthesis, showed a greater reduction in Pi resonance intensity in younger kidneys (62%) versus adult kidneys (38%).
Conclusions:
- Developing kidneys exhibit lower intracellular Pi concentrations.
- This lower intracellular Pi is associated with adaptive changes in renal Pi transport mechanisms.
- Intracellular Pi directly influences renal phosphate reabsorption capacity during kidney development.
Abstract:
During growth, the capacity for renal phosphate (Pi) reabsorption varies as a function of Pi demand. These changes occur in the absence of changes in extracellular concentration of Pi and are also observed in renal cells cultured in defined media. These findings suggest a direct regulatory effect of intracellular Pi on its transport systems. We postulate that a low intracellular Pi concentration [( Pi]i) occurs in the developing kidney as a consequence of differences in Pi metabolism between growing and mature cells and that a low [Pi]i, in turn, leads to adaptive changes in renal Pi transport. In order to assess this hypothesis, we used 31P-nuclear magnetic resonance (NMR) to measure the intracellular concentrations of NMR-visible Pi and phospho-metabolites and the rates of Pi turnover due to adenosine triphosphate (ATP) synthesis, in isolated perfused kidneys of 3- to 4-week-old and 12- to 13-week-old rats. The [Pi]i was lower (1.7 +/- 0.1 vs 2.7 +/- 0.1 mM, P less than 0.05) in kidneys of growing than of adult rats, while the ATP (2.9 +/- 0.3 vs 2.8 +/- 0.5 mM) and adenosine diphosphate (ADP) (-0.2 mM) concentrations were similar at the two ages, consistent with a high phosphorylation potential in the kidneys of the younger animals. Radiofrequency irradiation of the gamma-P of ATP resulted in reduction in the intensity of the Pi resonance of 62 +/- 5% in the newborn and 38 +/- 3% in the adult (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)