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 (P(i)) increases with dietary P(i) 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-P(i) 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-P(i) 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-P(i) diet (0.035 vs 0.017) (P < 0.01). Kinetics of renal Na(+)-dependent phosphate uptake in Hyp mice showed a Vmax of 1.00 +/- 0.01 and 0.46 +/- 0.02 nmoles/mg protein/15 sec in low- and control-P(i) diets, respectively (P < 0.01), whereas, Km values were 0.07 +/- 0.04 and 0.02 +/- 0.01, respectively. Similar kinetic analysis in renal BBM of normal mice showed a Vmax of 2.4 +/- 0.17 and 1.18 +/- 0.09 (P < 0.01) and Km of 0.07 +/- 0.03 and 0.08 +/- 0.03 on low and control P(i) diets, respectively. Similarly, low-P(i) 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 Vmax of 0.36 +/- 0.01 and 0.2 +/- 0.02 nmoles/mg protein/15 sec, (P < 0.01) and Km of 0.13 +/- 0.06 and 0.06 +/- 0.01 mM in low- and in control-P(i) diet, respectively. Kinetic analysis in jejunal BBM of normal mice showed a Vmax of 0.47 +/- 0.04 and 0.18 +/- 0.01 nmoles/mg protein/15 sec (P < 0.01) and Km of 0.16 +/- 0.04 and 0.11 +/- 0.01 in low- and control-P(i) diets, respectively. The data indicates that low-phosphate diet upregulates the Vmax of the renal and jejunal Na(+)-dependent phosphate cotransporter in the hypophosphatemic mice.
Nakagawa
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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2576.
Ghishan
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FK
D000222:Adaptation, Physiological; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D007015:Hypophosphatemia, Familial / Q000150:complications / Q000378:metabolism*; D066298:In Vitro Techniques; D007583:Jejunum / Q000378:metabolism* / Q000648:ultrastructure; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000172:deficiency* / Q000493:pharmacokinetics; D012279:Rickets / Q000209:etiology; D012964:Sodium / Q000494:pharmacology; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D015854:Up-Regulation
D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D012964:Sodium