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Am J Physiol Renal Physiol 289: F933-F938, 2005. First published June 7, 2005; doi:10.1152/ajprenal.00005.2005
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REPORT

Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1–/– renal proximal tubule cells and wild-type cells adapted to low-phosphate media

Rochelle Cunningham,1 Xiaofei E,1 Deborah Steplock,1 Shirish Shenolikar,2 and Edward J. Weinman1,3

1Department of Medicine, Department of Physiology, University of Maryland School of Medicine, and 3Medical Service, Department of Veterans Affairs Medical Center, Baltimore, Maryland; and 2Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina

Submitted 11 January 2005 ; accepted in final form 30 May 2005

ABSTRACT

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.

Na+/H+ exchanger regulatory factor-1; renal phosphate transport; sodium-dependent phosphate transporter IIa; mouse kidney


Address for reprint requests and other correspondence: E. J. Weinman, UMH, 22 S. Green St., Rm. N3W143, Baltimore, MD 21201 (e-mail: eweinman{at}medicine.umaryland.edu)




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