Low Phosphate Diet Upregulates the Renal and Intestinal Sodium-Dependent Phosphate Transporter in Vitamin D-Resistant Hypophosphatemic Mice

Renal and jejunal absorption of inorganic phosphate (P₁) increases with dietary P₁ restriction in the rat. The defect in Na⁺-dependent phosphate transporter has been localized to the kidney of the Hyp mice; however, the adaptation to low-P₁ diet in both kidney and jejunum of the Hyp mice has not been well characterized. Therefore, the current studies were designed to characterize the adaptation of renal and jejunal Na⁺-dependent phosphate transport in the Hyp mice and compare it with normal mice. Low-P₁ diet significantly increased the slope of the initial rate of renal brush border membrane (BBM) phosphate uptake compared with corresponding values in mice raised on control-P₁ diet (0.035 vs 0.017) (P < 0.01). Kinetics of renal Na⁺-dependent phosphate uptake in Hyp mice showed a V _max of 1.00 ± 0.01 and 0.46 ± 0.02 nmoles/mg protein/15 sec in low- and control-P₁ diets, respectively (P < 0.01), whereas, K_m values were 0.07 ± 0.04 and 0.02 ± 0.01, respectively. Similar kinetic analysis in renal BBM of normal mice showed a V _max of 2.4 ± 0.17 and 1.18 ± 0.09 (P < 0.01) and K _m of 0.07 ± 0.03 and 0.08 ± 0.03 on low and control P₁ diets, respectively. Similarly, low-P₁ diet significantly increased the slope of the initial rate of intestinal phosphate uptake (0.013 and 0.007) (P < 0.01). Kinetics of jejunal Na⁺-dependent phosphate uptake in Hyp mice showed a V_max of 0.36 ± 0.01 and 0.2 ± 0.02 nmoles/mg protein/15 sec, (P < 0.01) and K_m of 0.13 ± 0.06 and 0.06 ± 0.01 mM in low- and in control-P₁ diet, respectively. Kinetic analysis in jejunal BBM of normal mice showed a V _max of 0.47 ± 0.04 and 0.18 ± 0.01 nmoles/mg protein/15 sec (P < 0.01) and K_m of 0.16 ± 0.04 and 0.11 ± 0.01 in low- and control-P₁ diets, respectively. The data indicates that low-phosphate diet upregulates the V _max of the renal and jejunal Na⁺-dependent phosphate cotransporter in the hypophosphatemic mice.