Evidence for multiple effects of vitamin D3 on calcium absorption: response of rachitic chicks, with or without partial vitamin D3 repletion, to 1,25-dihydroxyvitamin D3.

The effects of vitamin D3 or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or both, on the relationship among calcium absorption, vitamin D-induced calcium-binding protein (CaBP), and phospholipid metabolism were examined. When 1,25(OH)2D3 was injected intracardially into D3-deficient chicks, both the stimulation of calcium absorption and the induction of the synthesis of CaBP occurred 2-4 hr later. When 1,25(OH)2D3 was injected into chicks partially repleted with D3, an earlier increase in calcium absorption was observed without a significant change in the concentration of CaBP already present in the duodenal mucosa. Other early events were an increased uptake of calcium by the intestinal tissue and an alteration in phospholipid metabolism. These and other observations support the proposal that at least two phases of calcium absorption are influenced by 1,25(OH)2D3--permeation of calcium across the brush border, and transfer of calcium through and out of the cell. The first phase responds more rapidly to 1,25(OH)2D3 than does the second phase, correlates with changes in phospholipid metabolism, and might not be dependent on de novo protein synthesis. The second phase correlates with CaBP synthesis and therefore is dependent on protein synthesis. Either the first phase or the second phase can constitute the limiting step in calcium absorption.