Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1-/- renal proximal tubule cells and wild-type cells adapted to low-phosphate media.
The present experiments using primary cultures from renal proximal tubule cells examine two aspects of the regulation of sodium-dependent phosphate transport and membrane sodium-dependent phosphate transporter (Npt2a) expression by parathyroid hormone (PTH). Sodium-dependent phosphate transport in proximal tubule cells from wild-type mice grown in normal-phosphate media averaged 4.4 +/- 0.5 nmol.mg protein(-1).10 min(-1) and was inhibited by 30.5 +/- 8.6% by PTH (10(-7) M). This was associated with a 32.7 +/- 5.2% decrease in Npt2a expression in the plasma membrane. Proximal tubule cells from Na(+)/H(+) exchanger regulatory factor-1 (NHERF-1)(-/-) mice had a lower rate of phosphate transport compared with wild-type cells and a significantly reduced inhibitory response to PTH. Wild-type cells incubated in low-phosphate media for 24 h had a higher rate of phosphate transport compared with wild-type cells grown in normal-phosphate media but a significantly blunted inhibitory response to PTH. These data indicate a role for NHERF-1 in mediating the membrane retrieval of Npt2a and the subsequent inhibition of phosphate transport in renal proximal tubules. These studies also suggest that there is a blunted phosphaturic effect of PTH in cells adapted to low-phosphate media.
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Related Subject Headings
- Urology & Nephrology
- Sodium-Hydrogen Exchangers
- Sodium
- Protein Kinase C
- Phosphoproteins
- Phosphates
- Parathyroid Hormone
- Mitogen-Activated Protein Kinases
- Mice, Knockout
- Mice, Inbred C57BL
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Urology & Nephrology
- Sodium-Hydrogen Exchangers
- Sodium
- Protein Kinase C
- Phosphoproteins
- Phosphates
- Parathyroid Hormone
- Mitogen-Activated Protein Kinases
- Mice, Knockout
- Mice, Inbred C57BL