Phosphophloretin sensitivity of rabbit renal NaPi-IIa and NaPi-Ia

Abstract

The effect of phosphorylated phloretins on Na+-dependent phosphate uptake into rabbit renal brush-border membrane vesicles (BBMV) was examined. Na+-dependent phosphate uptake into isolated rabbit cortex BBMV was sensitive to 2′-phosphophloretin (2′-PP) and 2′-phospho-4′,4,6′-trimethoxy phloretin (PTMP) in a dose-dependent and pH-dependent manner. PTMP inhibition of Na+-dependent phosphate uptake was maximum at alkali pH, and 2′-PP inhibition of Na+-dependent phosphate uptake was maximum at acidic pH. Increasing Na+concentrations did not increase PTMP inhibition of renal cortex BBMV Na+-dependent phosphate uptake at pH 6. The effect of phosphophloretins on Na+-dependent phosphate uptake was examined in BBMV isolated from purified proximal tubules and distal tubules. 2′-PP and PTMP inhibition of Na+-dependent phosphate uptake into BBMV isolated from purified proximal tubules was similar to the inhibition seen with BBMV from renal cortex. 2′-PP, but not PTMP, inhibited Na+-dependent phosphate uptake into BBMV isolated from purified distal tubules. The pH dependence of inhibition, the absence of PTMP inhibition of Na+-dependent phosphate uptake into distal tubule BBMV, and the inhibition of Na+-dependent phosphate uptake into distal tubule BBMV suggest that NaPi-Ia is 2′-PP sensitive and NaPi-IIa is PTMP sensitive.