Intestinal and renal adaptation to a low-Pi diet of type IINaPi cotransporters in vitamin D receptor- and 1αOHase-deficient mice

Intake of a low-phosphate diet stimulates transepithelial transport of P-i in small intestine as well as in renal proximal tubules. In both organs, this is paralleled by a change in the abundance of the apically localized NaPi cotransporters NaPi type IIa (NaPi-IIa) and NaPi type IIb (NaPi-IIb), respectively. Low-P-i diet, via stimulation of the activity of the renal 25-hydroxyvitamin-D-3- 1alpha-hydroxylase (1alphaOHase), leads to an increase in the level of 1,25-dihydroxy-vitamin D-3 [1,25(OH)(2)D]. Regulation of the intestinal absorption of P-i and the abundance of NaPi-IIb by 1,25( OH)(2)D has been supposed to involve the vitamin D receptor (VDR). In this study, we investigated the adaptation to a low-P-i diet of NaPi-IIb in small intestine as well as NaPi-IIa in kidneys of either VDR- or 1alphaOHase-deficient mice. In both mouse models, upregulation by a low-P-i diet of the NaPi cotransporters NaPi-IIa and NaPi-IIb was normal, i.e., similar to that observed in the wild types. Also, in small intestines of VDR- and 1alphaOHase-deficient mice, the same changes in NaPi-IIb mRNA found in wild-type mice were observed. On the basis of the results, we conclude that the regulation of NaPi cotransport in small intestine ( via NaPi-IIb) and kidney ( via NaPi-IIa) by low dietary intake of P-i cannot be explained by the 1,25(OH)(2)D-VDR axis.