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Published on: February 3, 2018
Role of intracellular phosphate in the regulation of renal phosphate transport during development
M Barac-Nieto1, H Corey, S M Liu
1Albert Einstein College of Medicine, Department of Pediatrics, Bronx, New York 10461.
Insights
Phosphate transport in kidneys is regulated by factors beyond intracellular phosphate levels. Growth hormone and bone mineralization inhibitors alter phosphate transport without changing intracellular phosphate concentrations.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Renal intracellular phosphate concentration ([Pi]i) correlates with age and diet, and inversely with phosphate transport (TRPi).
- Existing knowledge does not fully explain the high neonatal renal Na(+)-Pi cotransport capacity based solely on [Pi]i.
- The study investigates if factors other than [Pi]i mediate changes in TRPi due to altered phosphate demand.
Purpose of the Study:
- To determine if changes in renal tubular phosphate transport (TRPi) are mediated by factors other than intracellular phosphate concentration ([Pi]i).
- To investigate the role of growth hormone (GH) and bone mineralization inhibition in regulating TRPi.
Main Methods:
- TRPi measured in vivo; [Pi]i measured in perfused kidneys using nuclear magnetic resonance (NMR).
- Used genetically growth hormone-deficient dwarf rats and GH-treated rats.
- Used thyroparathyroidectomized (TPTX) Sprague-Dawley (SD) rats treated with etidronate (EHDP), a bone mineralization inhibitor.
Main Results:
- GH administration increased TRPi by 38% in dwarf rats without affecting [Pi]i.
- EHDP administration decreased TRPi by 52% in TPTX SD rats without affecting [Pi]i.
- Neither GH nor EHDP significantly altered [Pi]i levels.
Conclusions:
- In rats, alterations in renal tubular phosphate transport (TRPi) in response to changes in phosphate demand occur independently of significant changes in intracellular phosphate concentration ([Pi]i).
- Growth hormone and inhibition of bone mineralization influence TRPi through mechanisms not directly linked to intracellular phosphate levels.
Abstract:
Direct correlations have been observed between the renal intracellular concentration of phosphate ([Pi]i) and postnatal age (3-13 weeks in rats, 1-4 weeks in guinea pigs), as well as between the dietary supply of Pi and [Pi]i. In turn, [Pi]i was found to be inversely correlated with the renal tubular transport of phosphate (TRPi). However, age- and diet-related differences in [Pi]i alone do not explain the high capacity of Na(+)-Pi cotransport present in the kidney of the neonate. Therefore, we explored whether changes in TRPi induced by altering Pi demand (whole body growth or bone mineralization) are mediated by factors other than changes in [Pi]i. TRPi was measured in vivo and nuclear magnetic resonance-visible [Pi]i in perfused kidneys of 8-week-old genetically growth hormone (GH)-deficient and GH-treated dwarf rats and in 8-week-old thyroparathyroidectomized (TPTX) Sprague-Dawley (SD) rats treated or untreated with etidronate (EHDP), an inhibitor of bone mineralization. In dwarf rats, [Pi]i was 1.2 +/- 0.2 mM and TRPi 2.4 +/- 0.2 mumol/ml glomerular filtrate. In TPTX SD rats, [Pi]i was 1.6 +/- 0.2 mM and TRPi 4.2 +/- 0.3 mumol/ml glomerular filtrate. Administration of GH to dwarf rats resulted in increases in Pi transport of 38% +/- 8% (P < 0.05), while administration of EHDP to TPTX SD rats decreased TRPi by 52% +/- 7% (P < 0.05). Neither GH nor EHDP significantly affected [Pi]i. Thus, in the rat changes in TRPi due to alterations in Pi demand occur in the absence of significant changes in [Pi]i.(ABSTRACT TRUNCATED AT 250 WORDS)
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