Different effects of arsenate and phosphonoformate on P(i) transport adaptation in opossum kidney cells.
The main nonhormonal mechanism for controlling inorganic phosphate (P(i)) homeostasis is renal adaptation of the proximal tubular P(i) transport rate to changes in dietary phosphate content. Opossum kidney (OK) cell line is an in vitro renal model that maintains the ability of renal adaptation to the extracellular P(i) concentration. We have studied how two competitive inhibitors of P(i) transport, arsenate [As(V)] and phosphonoformate (PFA), affect adaptation to low and high P(i) concentrations. OK cells show very high affinity for As(V) (inhibitory constant, K(i) 0.12 mM) when compared with the rat kidney. As(V) very efficiently reversed the adaptation of OK cells to low P(i) (0.1 mM), whereas PFA induced adaptation similar to 0.1 mM P(i). Adaptation with 2 mM P(i) or As(V) was characterized by decreases in the maximal velocity (V(max)) of P(i) transport and an abundance of the NaPi-IIa P(i) transporter in the plasma membrane, shown by the protein biotinylation. Conversely, PFA and 0.1 mM P(i) increased the V(max) and transporter abundance. Changes in the V(max) were limited to a 50% variation, which was not paralleled by changes in the concentration of P(i) or of the inhibitor. OK cells are very sensitive to As(V), but the effects are reversible and noncytotoxic. These effects can be interpreted as As(V) being transported into the cell, thereby mimicking a high P(i) concentration. PFA blocks the uptake of P(i) but is not transported, and it therefore simulates a low P(i) concentration inside the cell. To conclude, a mathematical definition of the adaptation process is reported, thereby explaining the limited changes in P(i) transport V(max).
Villa-Bellosta
Ricardo
R
Laboratory of Molecular Toxicology, Univ. of Zaragoza, Zaragoza, Spain.
Sorribas
Víctor
V
D000818:Animals; D001149:Arsenates / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D017245:Foscarnet / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology* / Q000187:drug effects*; D009865:Oocytes; D009893:Opossums; D010758:Phosphorus / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism; D014981:Xenopus
D001149:Arsenates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D010758:Phosphorus; D017245:Foscarnet