Inhibition of human intestinal brush border membrane vesicle Na+ -dependent phosphate uptake by phosphophloretin derivatives

Abstract 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 ′ -PP ≫ 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.