Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis

• Published in: Pflügers Archiv 2010-02, Vol.459 (3), p.499-508
• Main Authors: Villa-Bellosta, Ricardo, Sorribas, Víctor
• Format: Article
• Language: English
• Subjects: Acidosis - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Diet; Human Physiology; Hydrogen-Ion Concentration; Kidney Tubules - cytology; Kidney Tubules - metabolism; Male; Membranes; Molecular Medicine; Neurosciences; Phosphates - deficiency; Rats; Rats, Sprague-Dawley; Receptors; Rodents; Sodium-Phosphate Cotransporter Proteins, Type IIc - metabolism; Sodium-Phosphate Cotransporter Proteins, Type III - metabolism; Transport Physiology; Xenopus laevis
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-009-0746-z

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 ≈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.