Luminal Phosphorus-responsive Epithelial Calcium Transport in the Intestine

Abstract

Intestinal calcium absorption is mediated by the vitamin D endocrine system, which responds to calcium demand in the body. Intestinal calcium absorption is the predominant source for maintenance of calcium homeostasis under a normal or positive calcium balance. Active transcellular calcium transport ensures appropriate intestinal absorption, and is regulated by 1,25(OH)₂D₃-vitamin D receptor (VDR) signaling. Vitamin D-dependent mechanisms have been well investigated using mice lacking VDR activity, which show reduction of both epithelial calcium channels and expression of cellular calcium binding protein which are directly controlled by 1α,25(OH)₂D₃. In contrast, dietary phosphate restriction simply increases calcium absorption in mice, regardless of 1,25(OH)₂D₃-VDR signaling. These mice demonstrated an improvement of bone mass, indicating a positive effect resulting from normalization of calcium balance. A possible explanation for these observations is that phosphate directly regulates transcellular calcium absorption, independent of the vitamin D endocrine system. Dietary phosphate restriction increased intestinal luminal ATP, likely stimulating transfer of calcium from luminal fluid to epithelial cells via the P2X ATP receptor. These findings suggest plausible mechanisms of transcellular calcium absorption in response to the dietary phosphate level.