Regulation of the rat intestinal phosphate transporters by dietary phosphate

Abstract

Elevated serum phosphate (Pi) remains a clinical challenge in patients with chronic kidney disease. However, Pi absorption mechanism in the small intestine is not fully understood. NaPi‐2b was identified as the main transporter responsible for intestinal Pi absorption. In mice NaPi‐2b expression concentrates mainly in the ileum. In contrast, rat NaPi‐2b mRNA and protein is expressed in jejunum and duodenum with negligible amounts in ileum, a pattern similar to humans. We report expression of another NaPi transporter showing a similar expression profile: Pit‐1. We characterized intestinal NaPi transport regulation by dietary Pi during chronic and acute alterations in dietary Pi. Chronic low Pi diet induces an increase in jejunal NaPi transport activity and increases in BBM NaPi‐2b protein and mRNA abundance. In contrast, we found an unexpected regulatory response in rats switched from a chronic low Pi diet to a high Pi diet acutely: Duodenum BBM NaPi uptake and NaPi‐2b protein is highly up‐regulated. Moreover, under this acute condition serum Pi is markedly increased as early as 2 hours after feeding. We propose that increased transcellular Pi transport mediated by NaPi‐2b is inducing the unfavorable increase of serum Pi under this condition. Moreover, Pit‐1expression in this tissue could also be playing a role in the intestinal Pi absorption in rats.