Effect of vitamin D metabolites and analogs on renal and intestinal calbindin-D in the rat.
The effects on renal and intestinal calbindin-D of vitamin D3 metabolites and synthetic 20-epi-vitamin D3 analogs with different calcemic actions were examined in Wistar rats. The compounds were administered intraperitoneally once daily for 5 days. The dosages of the metabolites were 1,25-(OH)2D3 0.01, 0.05, 0.1, and 0.4 microg/kg x d, 24,25-(OH)2D3 0.1, 1 and 10 microg/kg x d, and 25-(OH)D3 10 and 400 microg/kg x d. The dosage of the synthetic analogs were MC903 0. 1, 10, and 100 microg/kg x d, EB1213 0.1 and 10 microg/kg x d, KH1060 0.1 and 0.4 microg/kg x d, and GS1725 0.01 and 0.1 microg/kg x d. Two control groups had either vehicle alone or no treatment. N = 8 in each group. 1,25-(OH)2D3 increased renal and intestinal calbindin-D levels, induced hypercalcemia, and suppressed plasma PTH and magnesium concentrations. 24,25-(OH)2D3 increased intestinal calbindin-D9k and plasma calcium, but had no effect on renal calbindin-D28k, plasma PTH, and magnesium. The dosage of 24, 25-(OH)2D3 that was required to increase plasma calcium was larger than the dosage required to increase intestinal calbindin-D9k. 25-(OH)D3 did not change the calcium metabolic parameters. MC903, a low calcemic analog with a relative high affinity for the vitamin D receptor and a short half-life, increased renal calbindin-D28k without increasing ionized calcium or intestinal calbindin-D9k. EB1213, an analog with a reduced calcemic action and short half-life, increased renal calbindin-D28k and ionized calcium without increasing intestinal calbindin-D9k. The effect of the high calcemic vitamin D analogs KH1060 and GS1725 on calbindin-D was directly related to their calcemic activity. In conclusion, these results demonstrate that 24,25-(OH)2D3 increases intestinal calbindin-D9k, but has no effect on renal calbindin-D28k, that low calcemic analogs may increase renal calbindin-D28k without increasing intestinal calbindin-D9k, and that the effect of high calcemic analogs on calbindin-D is directly related to their calcemic activity.
Hemmingsen
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Department of Nephrology P-2131, Rigshospitalet, 9, Blegdamsvej, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Staun
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Lewin
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Nielsen
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Olgaard
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K
D000279:Administration, Cutaneous; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002117:Calcitriol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D014807:Vitamin D; C055085:calcipotriene; D002117:Calcitriol