Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis
- 1 November 2009
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 20 (11), 2348-2358
- https://doi.org/10.1681/asn.2009050559
Abstract
Intestinal phosphate absorption occurs through both a paracellular mechanism involving tight junctions and an active transcellular mechanism involving the type II sodium-dependent phosphate cotransporter NPT2b (SLC34a2). To define the contribution of NPT2b to total intestinal phosphate absorption, we generated an inducible conditional knockout mouse, Npt2b−/− (Npt2bfl/fl:Cre+/−). Npt2b−/− animals had increased fecal phosphate excretion and hypophosphaturia, but serum phosphate remained unchanged. Decreased urinary phosphate excretion correlated with reduced serum levels of the phosphaturic hormone FGF23 and increased protein expression of the renal phosphate transporter Npt2a. These results demonstrate that the absence of Npt2b triggers compensatory renal mechanisms to maintain phosphate homeostasis. In animals fed a low phosphate diet followed by acute administration of a phosphate bolus, Npt2b−/− animals absorbed approximately 50% less phosphate than wild-type animals, confirming a major role of this transporter in phosphate regulation. In vitro analysis of active phosphate transport in ileum segments isolated from wild-type or Npt2b−/− mice demonstrated that Npt2b contributes to >90% of total active phosphate absorption. In summary, Npt2b is largely responsible for intestinal phosphate absorption and contributes to the maintenance of systemic phosphate homeostasis.Keywords
This publication has 41 references indexed in Scilit:
- Targeted deletion of the tybe IIb Na+-dependent Pi-co-transporter, NaPi-IIb, results in early embryonic lethalityBiochemical and Biophysical Research Communications, 2009
- Type IIc Sodium–Dependent Phosphate Transporter Regulates Calcium MetabolismJournal of the American Society of Nephrology, 2009
- Active Intestinal Calcium Transport in the Absence of Transient Receptor Potential Vanilloid Type 6 and Calbindin-D9kEndocrinology, 2008
- Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorptionProceedings of the National Academy of Sciences of the United States of America, 2007
- Type II Na+-Pi Cotransporters in Osteoblast Mineral Formation: Regulation by Inorganic PhosphateCellular Physiology and Biochemistry, 2007
- Mutations in SLC34A2 Cause Pulmonary Alveolar Microlithiasis and Are Possibly Associated with Testicular MicrolithiasisAmerican Journal of Human Genetics, 2006
- Intestinal Na-Picotransporter adaptation to dietary Picontent in vitamin D receptor null miceAmerican Journal of Physiology-Renal Physiology, 2004
- Cardiac calcification in adult hemodialysis patients: A link between end-stage renal disease and cardiovascular disease?Journal of the American College of Cardiology, 2002
- Cloning and Functional Characterization of a Sodium-Dependent Phosphate Transporter Expressed in Human Lung and Small IntestineBiochemical and Biophysical Research Communications, 1999
- PROGRESS AND RATE OF ABSORPTION OF RADIOPHOSPHORUS THROUGH THE INTESTINAL TRACT OF RATSCanadian Journal of Biochemistry and Physiology, 1961