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6349656 
Journal Article 
Adaptation of Opossum Kidney Cells to Luminal Phosphate: Effects of Phosphonoformic Acid and Kinase Inhibitors 
Thomas, L; Wagner, CA; Biber, J; Hernando, N 
2016 
1 
Kidney and Blood Pressure Research
ISSN: 1420-4096
EISSN: 1423-0143 
Kidney & Blood Pressure Research 
41 
3 
298-310 
English 
27165344 
WOS:000378796200008 
Background/Aims: 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. (C) 2016 The Author(s) Published by S. Karger AG, Basel 
Research & Experimental Medicine; Proximal tubule, Reabsorption of phosphate, Phosphate sensing, OK cells; p-i cotransporter, parathyroid-hormone inhibition, proximal tubule; cells, dietary phosphate, ok cells, na+/phosphate cotransport, cellular; mechanisms, renal adaptation, pth secretion, brush-border