X-LINKED HYPOPHOSPHATEMIC GY MICE - RENAL TUBULAR MAXIMUM FOR PHOSPHATE VS BRUSH-BORDER TRANSPORT AFTER LOW-P DIET

We examined the effect of the X-linked hypophosphatemic Gy mutation on the maximal renal tubular reabsorption of phosphate (Tmp) and compared the effects of phosphate deprivation on both Tmp and Na+-dependent phosphate transport in renal brush-border membrane vesicles (BBMV). Adult female normal and Gy mice were fed a control (1.0% P) or low-phosphate (0.03% P) diet for 5 days. For Tmp measurement, anesthetized mice were infused intravenously with [H-3]inulin and increasing increments of phosphate (0, 0.27, 0.54, and 1.08 mu mol/min). Tmp was significantly reduced in Oy mice on the control diet. Normal mice responded to the low-phosphate diet by raising their Tmp [2.35 +/- 0.12 (n = 9) vs. 3.71 +/- 0.16 (n = 9) mu mol/ml glomerular filtrate, mean +/- SE, P < 0.001], whereas in Gy mice, the change was not significant [1.46 +/- 0.10 (n = 10) vs. 1.70 +/- 0.11 (n = 10)]. In contrast, Gy mice did respond to phosphate restriction by increasing the initial-rate Na+-dependent phosphate transport in the renal BBMV [314 +/- 11 (n = 5) vs. 1,105 +/- 157 (n = 5) pmol.mg protein(-1).6 s(-1), P < 0.01] as did normal mice [583 +/- 64 (n = 5) vs. 1,692 +/- 203 (n = 5) pmol.mg protein(-1).6 s(-1), P < 0.01]. In conclusion, the adaptive increase in Na+-phosphate cotransport in the brush-border membrane of the proximal tubule is not sufficient for the overall increase in Tmp in the whole kidney in response to dietary phosphate deprivation.