The Effects of 24R, 25-dihydroxyvitamin D3 and 24S, 25-dihydroxyvitamin D3 on Phosphate Transport in Chicks In Vivo

Abstract

Previous work in this laboratory has indicated that 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] inhibits rapid, 1,25-dihuydroxyvitamin D3 [1,25(OH)2D3] stimulated phosphate uptake in isolated intestinal cells and perfused duodenal loops. Studies were undertaken to determine if 24,25(OH)2D3 had a similar effect in vivo. 24,25(OH)2D3 has two isomers which are 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] and 24S,25-dihydroxyvitamin D3 [24S,25(OH)2D3]., which we studied separately and tested over a time course of 1, 5, 10, 15 and 18 hours after steroid using chicks on regular diet, but fasted, and chicks on a lower vitamin D diet. All chicks were anesthetized prior to surgical exposure of the duodenal loop and injection of a solution containing H3 32PO4 into the lumen. Blood was then collected and serum prepared to determine transport of the radionuclide by liquid scintillation counting. An initial time course study of phosphate transport determined that 3 to 9 min of absorption in vivo was in a linear range, as judged by serum levels of radioactivity. Chicks were then injected with either 200 μg 24R,25(OH)2D3, 20 μg 24S,25(OH)2D3 or vehicle for control groups within the same time course studies. We found that the isomers had different effects on phosphate absorption. 24R,25(OH)2D3 had a hypophosphatemic effect in vivo. The serum levels of radionuclide revealed hypophosphatemic effects at 1, 5, 15 and 18 hours time points with a decrease of 56%, 42%, 39% and 43%, respectively, (P< 0.05) compared with controls. In contrast, 24S,25(OH)2D3 stimulated intestinal phosphate absorption at the five hour time point by 64%, but had no other effects at the other time points tested. We conclude that 24R,25(OH)2D3, which is made when dietary vitamin D levels are high, inhibits phosphate transport from the intestine, while 24S,25(OH)2D3 lacks activity in vivo. Keywords: Chick, hypocalcem, hypophosphatemia, intestine, in vivo, phosphate absorption, phosphate transport, serum phosphate, vitamin D, 24S, 25-dihydroxyvitamin D, 24R, 25-dihydroxyvitamin D, phosphate transport, 25-dihydroxyvitamin D3.