Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis

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, w...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2009-11, Vol.20 (11), p.2348-2358
Main Authors: SABBAGH, Yves, O'BRIEN, Stephen P, WENPING SONG, BOULANGER, Joseph H, STOCKMANN, Adam, ARBEENY, Cynthia, SCHIAVI, Susan C
Format: Article
Language:English
Subjects:
Absorption
Animals
Basic Research
Biological and medical sciences
Biological Transport, Active
Homeostasis - physiology
Ileum - metabolism
Medical sciences
Mice
Nephrology. Urinary tract diseases
Phosphates - metabolism
Sodium-Phosphate Cotransporter Proteins, Type IIb - physiology
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Summary: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(-/-) (Npt2b(fl/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.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2009050559