Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport.

Abstract

19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) 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-norD(2) or 1,25(OH)(2)D(3). 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)(2)D(3) 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-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). 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)(2)D(3) 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-norD(2), 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)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.

• Authors: Alex J Brown, Jane Finch, Eduardo Slatopolsky
• Journal: The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 139 Issue 5 Pg. 279-84 (May 2002) ISSN: 0022-2143 [Print] United States
• PMID: 12032488 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calbindins
• Calcium Channels
• Calcium Channels, T-Type
• Calcium, Dietary
• Cation Transport Proteins
• Ergocalciferols
• Phosphates
• Phosphorus, Dietary
• RNA, Messenger
• S100 Calcium Binding Protein G
• S100g protein, rat
• TRPV Cation Channels
• TRPV5 protein, rat
• paricalcitol
• Plasma Membrane Calcium-Transporting ATPases
• Atp2b1 protein, rat
• Calcium-Transporting ATPases
• Calcitriol
• Calcium

Topics

• Animals
• Blotting, Northern
• Calbindins
• Calcitriol (administration & dosage, pharmacology)
• Calcium (blood, pharmacokinetics)
• Calcium Channels (genetics)
• Calcium Channels, T-Type (genetics)
• Calcium, Dietary (pharmacokinetics)
• Calcium-Transporting ATPases (genetics)
• Cation Transport Proteins
• Ergocalciferols (administration & dosage, pharmacology)
• Female
• Gene Expression Regulation (drug effects)
• Intestinal Absorption (drug effects, genetics)
• Phosphates (pharmacokinetics)
• Phosphorus, Dietary (pharmacokinetics)
• Plasma Membrane Calcium-Transporting ATPases
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• S100 Calcium Binding Protein G (genetics)
• TRPV Cation Channels