Intestinal Na-Pi cotransporter adaptation to dietary Pi content in vitamin D receptor null mice

Abstract

Recent studies suggest that vitamin D may play a role in intestinal Na+-dependent phosphate transport adaptation to variable levels of dietary Pi. Therefore, the goal of the current study was to assess Na+-dependent Pi cotransport activity in transgenic mice to determine whether vitamin D is an essential mediator of this process. Intestinal brush-border membrane (BBM), Na+-dependent Pi cotransport activity was significantly decreased in vitamin D receptor (VDR) null [VDR (−/−)] mice compared with wild-type (VDR+/+) mice. While intestinal Na-Pi cotransporter (type IIb) mRNA levels were similar in VDR (−/−) and VDR (+/+) mice, type IIb Na-Pi cotransporter protein expression was markedly suppressed in VDR (−/−) mice compared with VDR (+/+) mice. Furthermore, Na-Pi cotransport activity in renal BBM was similar in VDR (−/−) and VDR (+/+) mice, but type IIa Na-Pi cotransporter protein expression was decreased in VDR (−/−) mice. After administration of a low-Pi diet, type IIb protein expression was significantly increased in VDR (+/+) and VDR (−/−) mice, and type IIb protein expression was present in the intestinal BBM of VDR (−/−) mice. These data demonstrate that intestinal Na-Pi cotransport adaptation to a low-Pi diet occurs independently of vitamin D.