A phosphorylated phloretin derivative. Synthesis and effect on intestinal Na(+)-dependent phosphate absorption.
2'-Phosphophloretin (2'-PP), a phosphorylated derivative of the plant chalcone, was synthesized. The effect of 2'-PP, on Na(+)-dependent phosphate uptake into intestinal brush-border membrane vesicles (BBMV) isolated from rabbit and rat duodenum and jejunum was examined. 2'-PP decreased Na(+)-dependent phosphate uptake into rabbit BBMV with an IC(50) of 55 nM and into rat BBMV with an IC(50) of 58 nM. 2'-PP did not affect Na(+)-dependent glucose, Na(+)-dependent sulfate, or Na(+)-dependent alanine uptake by rabbit intestinal BBMVs. 2'-PP inhibition of rabbit intestinal BBMV Na(+)-dependent phosphate uptake was sensitive to external phosphate concentration, suggesting that 2'-PP inhibition of Na(+)-dependent phosphate uptake was competitive with respect to phosphate. Binding of [(3)H]2'-PP to rabbit intestinal BBMV was examined. Binding of [(3)H]2'-PP was Na(+)-dependent with a K(0.5) for Na(+)(Na(+) concentration for 50% 2'-PP binding) of 30 mM. The apparent K(s) for Na(+)-dependent [(3)H]2'-PP binding to rabbit BBMVs was 58 nM in agreement with the IC(50) for 2'-PP inhibition of Na(+)-dependent phosphate uptake. These results indicate that 2'-PP bound to rabbit or rat intestinal BBMV Na(+)-phosphate cotransporter and inhibited Na(+)-dependent phosphate uptake. In rats treated with 2'-PP by daily gavage, the effect of 2'-PP on serum phosphate, serum glucose, and serum calcium was examined. In a concentration-dependent manner, 2'-PP reduced serum phosphate by 45% 1 wk after starting treatment. 2'-PP did not alter serum calcium or serum glucose. The apparent IC(50) for 2'-PP in vivo was 3 microM.
Peerce
Brian E
BE
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-0641, USA. BPeerce@UTMB.edu
Clarke
Rebecca
R
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000097:blood; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism; D010693:Phloretin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters / Q000037:antagonists & inhibitors
C466384:2'-phosphophloretin; D001786:Blood Glucose; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D012964:Sodium; D010693:Phloretin; D002118:Calcium