Abstract
19-Nor-1,25-dihydroxyvitamin D2 (19-norD2) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH]2D3), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD2 is less active than 1,25(OH)2D3 in stimulating bone resorption. In this study, we compared the potencies of 19-norD2 and 1,25(OH)2D3 in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD2 or 1,25(OH)2D3. Calcium absorption increased from 16.5% ± 7.8% in vehicle-treated rats to 27.5% ± 7.2% in rats given 10 ng/day 1,25(OH)2D3 and to 21.6% ± 3.9%, 26.2% ± 5.5%, and 27.4% ± 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD2, respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)2D3 and 100 ng 19-norD2. Similar results were obtained for phosphate absorption, with an increase from 28.2% ± 5.5% in vehicle-treated rats to 40.2% ± 4.7% in rats given 10 ng/day 1,25(OH)2D3 and to 32.9% ± 2.2%, 36.2% ± 4.5%, and 36.8% ± 3.8% in rats given 10, 50, and 100 ng/day 19-norD2, respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)2D3 or 19-norD2 revealed that 19-norD2 was less potent than 1,25(OH)2D3 in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD2 can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption. (J Lab Clin Med 2002;139:279-84)
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