Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3

In a study of the rat intestinal P-i transport system, an activator protein for rat Na/P-i co-transport system (PiUS) was isolated and characterized. We also investigated the effects of restriction of vitamin D and P-i (two of the most important physiological and pathophysiological regulators of P-i absorption in the small intestine) on intestinal P-i transport activity and the expression of Na/P-i co-transporters that are expressed in rat small intestine, Rat PiUS encodes a 424-residue protein with a calculated molecular mass of 51 463 Da. The microinjection of rat PiUS into Xenopus oocytes markedly stimulated Na+-dependent P-i cotransport activity. In rats fed with a low-P-i diet, Na+-dependent P-i co-transport activity was increased approx. 2-fold compared with that of rats fed a normal P-i diet. Kinetic studies demonstrated that this increased activity was due to an elevation of V-max but not K-m. The PiUS mRNA levels showed an approximate doubling in the rats fed with the low-P-i diet compared with those fed with the normal P-i diet. In addition, after the administration of 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] to vitamin-D-deficient animals, the P-i uptake was significantly increased in the Na+-dependent component in the brush border membrane vesicle (BBMV) at 24 and 48 h. In addition, we found a further high-affinity Na/P-i co-transport system in the BBMV isolated from the vitamin :D-replete animals. The levels of type III Na/P-i cotransporter PiT-2 mRNA were increased 24 and 48 h after 1,25(OH)(2)D-3 administration to vitamin D-deficent animals, whereas PiUS and the type IIb Na/P-i co-transporter mRNA levels were unchanged. In conclusion, we first cloned a rat activator protein, PiUS, and then studied its role along with that of other type III Na/P-i co-transporters. PiUS and PiT-2 might be important components in the regulation of the intestinal P-i transport system by P-i restriction and 1,25-(OH)(2)D-3.