Document Detail


Different effects of arsenate and phosphonoformate on P(i) transport adaptation in opossum kidney cells.
MedLine Citation:
PMID:  19553564     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
Ricardo Villa-Bellosta; V??ctor Sorribas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-24
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  297     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-07     Completed Date:  2009-10-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C516-25     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Toxicology, Univ. of Zaragoza, Zaragoza, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenates / pharmacology*
Cell Line
Dose-Response Relationship, Drug
Foscarnet / pharmacology*
Kidney / cytology*,  drug effects*
Oocytes
Opossums
Phosphorus / metabolism*
Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism
Xenopus
Chemical
Reg. No./Substance:
0/Arsenates; 0/Sodium-Phosphate Cotransporter Proteins, Type IIa; 4428-95-9/Foscarnet; 7723-14-0/Phosphorus

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