Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives.
Hyperphosphatemia and II(o) hyperparathyroidism are common and severe complications of chronic renal failure. Reduced dietary phosphorus has been shown to be an effective treatment in reducing serum phosphate and serum PTH. 2(')-Phosphophloretin inhibited small intestine apical membrane Na(+)/phosphate cotransport and reduced serum phosphate in adult rats. 2(')-PP and phosphoesters of phloretin were tested for inhibition of human small intestine brush border membrane alkaline phosphatase activity and for inhibition of Na(+)-dependent phosphate uptake. The IC(50)'s for inhibition of alkaline phosphatase suggested an order of inhibitory potency of 4-PP > phloretin > 4(')-PP > 2(')-PP. Inhibition of Na(+)-dependent phosphate uptake followed the sequence 2(')-PPz.Gt;4(')-PP > 4-PP > phloretin. These results are consistent with 2(')-PP being a specific inhibitor of human intestinal brush border membrane Na(+)/phosphate cotransport.
Peerce
Brian E
BE
Department of Physiology and Biophysics, University of Texas Medical Branch, 12th and Mechanic, 2.200 Basic Science Bldg., Galveston, TX 77555-0641, USA. bpeerce@UTMB.edu
Fleming
R Y Declan
RY
Clarke
Rebecca D
RD
D000818:Animals; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism*; D015394:Molecular Structure; D010693:Phloretin / Q000031:analogs & derivatives / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors; D022161:Transport Vesicles / Q000378:metabolism*
D010710:Phosphates; D012964:Sodium; D010693:Phloretin