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

J Lab Clin Med. 2002 May;139(5):279-84. doi: 10.1067/mlc.2002.122819.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Calbindins
  • Calcitriol / administration & dosage
  • Calcitriol / pharmacology*
  • Calcium / blood
  • Calcium / pharmacokinetics*
  • Calcium Channels / genetics
  • Calcium Channels, T-Type / genetics
  • Calcium, Dietary / pharmacokinetics*
  • Calcium-Transporting ATPases / genetics
  • Cation Transport Proteins
  • Ergocalciferols / administration & dosage
  • Ergocalciferols / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption / drug effects*
  • Intestinal Absorption / 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

Substances

  • 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