1,25(OH) 2 vitamin D 3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Intestinal absorption of phosphate is stimulated by 1,25(OH)$_{2}$ vitamin D$_{3.}$ At least two distinct mechanisms underlie phosphate absorption in the gut, an active transcellular transport requiring the Na$^{+}$ /phosphate cotransporter NaPi-IIb/Slc34a2, and a poorly characterized paracellular passive pathway. 1,25(OH)$_{2}$ vitamin D$_{3}$ stimulates NaPi-IIb expression and function and loss of NaPi-IIb reduces intestinal phosphate absorption. However, it is remains unknown whether NaPi-IIb is the only target for hormonal regulation by 1,25(OH)$_{2}$ vitamin D$_{3}$ . Here we compared the effects of intraperitoneal administration of 1,25(OH)$_{2}$ vitamin D$_{3}$ (2 days, once per day) in wild type and intestinal-specific Slc34a2 deficient mice, and analyzed trans- vs paracellular routes of phosphate absorption. We found that treatment stimulated active transport of phosphate only in jejunum of wild type mice, though NaPi-IIb protein expression was upregulated in jejunum and ileum . In contrast, 1,25(OH)$_{2}$ vitamin D$_{3}$ administration had no effect in Slc34a2 deficient mice, suggesting that the hormone specifically regulates NaPi-IIb expression. In both groups, 1,25(OH)$_{2}$ vitamin D$_{3}$ elicited the expected increase of plasma FGF23 and reduction of PTH. Treatment resulted in hyperphosphaturia (and hypercalciuria) in both genotypes, though mice remained normophosphatemic. While increased intestinal absorption and higher FGF23 can trigger the hyperphosphaturic response in wild types, only the second one can explain the renal response in Slc34a2 deficient mice. Thus, 1,25(OH)$_{2}$ vitamin D$_{3}$ stimulates intestinal phosphate absorption by acting on the active transcellular pathway mostly mediated by NaPi-IIb while the paracellular pathway appears not to be affected. Intestinal absorption of phosphate proceeds via an active/transcellular route mostly mediated by NaPi-IIb/Slc34a2 and a poorly characterized passive/paracellular pathway. Intestinal phosphate absorption and expression of NaPi-IIb ...