HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/C516    most recent 00186.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Villa-Bellosta, R. Articles by Sorribas, V. PubMed PubMed Citation Articles by Villa-Bellosta, R. Articles by Sorribas, V.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Different effects of arsenate and phosphonoformate on P_i transport adaptation in opossum kidney cells

Laboratory of Molecular Toxicology, University of Zaragoza, Zaragoza, Spain

Submitted 30 April 2009 ; accepted in final form 22 June 2009

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 velociy (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.

phosphate transport; inorganic phosphate deprivation; NaPi-IIa; renal inorganic phosphate adaptation; inorganic phosphate reabsorption