Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis.
The role of four Pi transporters in the renal handling of Pi was analyzed using functional and molecular methods. The abundance of NaPi-IIa, NaPi-IIc, and Pit-2 was increased by 100% in kidney from rats on a 0.1% Pi diet, compared to a 0.6% Pi diet. Pit-1 was not modified. Type II-mediated Pi uptake in Xenopus oocytes increased as the pH of the uptake medium increased, and the opposite occurred with Pit-1 and Pit-2. At pH 6.0, Pi uptake mediated through type II was approximately 10% of the uptake at pH 7.5, but the uptake through Pit-2 was 250% of the activity at pH 7.5. Real brush-border membrane vesicles (BBMV) responded to pH changes following the same pattern as type II transporters. Adaptation to a 0.1% Pi diet was accompanied by a 65% increase in the V (max) of BBMV Pi transport at pH 7.5, compared to a 0.6% Pi diet. The increase was only 11% at pH 6.0. Metabolic acidosis increased the expression of NaPi-IIc and Pit-2 in animals adapted to a low Pi diet, and phosphaturia was only observed in control diet animals. The combination of the pH effect, Pi adaptation, and metabolic acidosis suggests very modest involvement of Pit-2 in renal Pi handling. Real-time PCR and mathematical analyses of transport findings suggest that NaPi-IIa RNA accounts for 95% of all Pi transporters and that type II handles 97% of Pi transport at pH 7.5 and 60% of Pi transport at pH 6.0, depending on the pH and the physiological conditions.
Laboratory of Molecular Toxicology, Veterinary Faculty, University of Zaragoza, Calle Miguel Servet 177, 50013 Zaragoza, Spain. rvilla@unizar.es
Ricardo
R
Villa-Bellosta
Víctor
V
Sorribas
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D004032:Diet; D006863:Hydrogen-Ion Concentration; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008297:Male; D010710:Phosphates / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000378:metabolism*; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000378:metabolism*; D014982:Xenopus laevis
D010710:Phosphates; C493566:Slc20a2 protein, rat; C493564:Slc34a3 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc