Sulfate inhibits [14C]phosphonoformic acid binding to renal brush-border membranes.
To examine the specificity of the phosphonoformic acid (PFA) interaction with the Na(+)-dependent phosphate transporter of mouse renal brush-border membrane vesicles, we compared the effects of anions on Na(+)-dependent [14C]PFA binding and Na(+)-dependent phosphate transport. Inhibition of PFA binding was achieved by PFA (% control = 0 +/- 1), sulfate (15 +/- 2), arsenate (35 +/- 1), phosphate (59 +/- 2), and nitrate (68 +/- 4), whereas inhibition of phosphate transport was only apparent with phosphate (0 +/- 1), PFA (22 +/- 4), and arsenate (37 +/- 5). Succinate and gluconate had no effect on either Na(+)-dependent process. Under conditions where Na(+)-dependent PFA binding was maximally inhibited by phosphate (% control = 65 +/- 4), further inhibition could be achieved by sulfate (26 +/- 5%). Na(+)-dependent PFA binding was competitively inhibited by phosphate (apparent Ki = 8.9 +/- 1.2 mM) and noncompetitively inhibited by sulfate (apparent Ki = 2.6 +/- 0.5 mM). We found that PFA inhibited Na(+)-dependent sulfate transport (50% inhibition at 9 mM PFA) as well as Na(+)-dependent phosphate transport (50% inhibition at 0.5 mM PFA). We also examined the pH dependence of Na(+)-dependent PFA binding and Na(+)-dependent phosphate and sulfate transport. PFA binding was optimal at pH = 7.4, whereas phosphate transport increased with increasing pH, and sulfate transport increased with decreasing pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Tenenhouse
H S
HS
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
Lee
J
J
D000818:Animals; D002250:Carbon Radioisotopes; D017245:Foscarnet; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D010710:Phosphates / Q000494:pharmacology; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D010710:Phosphates; D013431:Sulfates; D017245:Foscarnet; D012964:Sodium; D010746:Phosphonoacetic Acid