title: Adaptation of Opossum Kidney Cells to Luminal Phosphate: Effects of Phosphonoformic Acid and Kinase Inhibitors.
abstract: OBJECTIVE
  Renal reabsorption of inorganic phosphate (Pi) is mediated by SLC34 and SLC20 Na+/Pi-cotransporters the abundance of which is under hormonal control. Extracellular Pi itself also regulates the expression of cotransporters and the concentration of Pi-regulating hormones, though the signaling pathways are largely unknown. Here, we explored the mechanisms that allow renal proximal cells to adapt to changes in the concentration of Pi.
  
  
  METHODS
  opossum kidney (OK) cells, a model of proximal epithelia, were incubated with different concentrations of Pi in the absence/presence of phosphonoformic acid (PFA), a Pi-analogue and SLC34-inhibitor, and of inhibitors of kinases involved in hormonal control of Pi-homeostasis; cells cultured in normal media were treated with uncouplers of oxidative phosphorylation. Then, the intracellular concentration of ATP and/or the Pi-transport capacity of the cultures were analyzed.
  
  
  RESULTS
  luminal Pi regulates the Pi-transport and the intracellular ATP levels. Changes in ATP seem secondary to alterations in Pi-transport, rather than ATP acting as a signal. Adaptation of Pi-transport to high Pi was not mimicked by PFA. Transport adaptation was blocked by PFA but not by kinase inhibitors.
  
  
  CONCLUSIONS
  in OK cells, adaptation of Pi-transport to luminal Pi does not depend on the same signaling pathways involved in hormonal regulation.
authors.affiliation: NCCR Kidney.CH and Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Linto
authors.initials: L
authors.lastname: Thomas
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.forename: Jürg
authors.initials: J
authors.lastname: Biber
authors.forename: Nati
authors.initials: N
authors.lastname: Hernando
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D017245:Foscarnet / Q000037:antagonists & inhibitors; D007668:Kidney / Q000166:cytology*; D007687:Kidney Tubules, Proximal / Q000166:cytology; D009893:Opossums; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D050610:Sodium-Phosphate Cotransporter Proteins, Type II / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D010710:Phosphates; D047428:Protein Kinase Inhibitors; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D017245:Foscarnet; D000255:Adenosine Triphosphate