title: Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1-/- renal proximal tubule cells and wild-type cells adapted to low-phosphate media.
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.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Cunningham
authors.forename: Xiaofei
authors.initials: X
authors.lastname: E
authors.forename: Deborah
authors.initials: D
authors.lastname: Steplock
authors.forename: Shirish
authors.initials: S
authors.lastname: Shenolikar
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinman
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media; D000242:Cyclic AMP / Q000096:biosynthesis; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D010281:Parathyroid Hormone / Q000502:physiology*; D010710:Phosphates / Q000172:deficiency / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000096:biosynthesis; D012964:Sodium / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers
chemical_list: D003470:Culture Media; D010281:Parathyroid Hormone; D010710:Phosphates; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D012964:Sodium; D000242:Cyclic AMP; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases