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 D-3 metabol ites and synthetic 20-epi-vitamin D-3 analogs with different calcemic actions were examined in Wistar rats. The compounds were administered intraperitoneally once daily for 5 days. The dosages of the metabolite s were 1,25-(OH)(2)D-3 0.01, 0.05, 0.1, and 0.4 mu g/kg x d, 24,25-(OH )(2)D-3 0.1, 1 and 10 mu g/kg x d, and 25-(OH)D-3 10 and 400 mu g/kg x d. The dosage of the synthetic analogs were MC903 0.1, 10, and 100 mu g/kg x d, EB1213 0.1 and 10 mu g/kg x d, KH1060 0.1 and 0.4 mu g/kg x d, and GS1725 0.01 and 0.1 mu g/kg x d. Two control groups had either vehicle alone or no treatment. N = 8 in each group. 1,25-(OH)(2)D-3 i ncreased renal and intestinal calbindin-D levels, induced hypercalcemi a, and suppressed plasma PTH and magnesium concentrations. 24,25-(OH)( 2)D-3 increased intestinal calbindin-D9k and plasma calcium, but had n o effect on renal calbindin-D28k, plasma PTH, and magnesium. The dosag e of 24,25-(OH)(2)D-3 that was required to increase plasma calcium was larger than the dosage required to increase intestinal calbindin-D9k. 25-(OH)D-3 did not change the calcium metabolic parameters. MC903, a low calcemic analog with a relative high affinity for the vitamin D re ceptor and a short half-life, increased renal calbindin-D28k without i ncreasing ionized calcium or intestinal calbindin-D9k. EB1213, an anal og with a reduced calcemic action and short half-life, increased renal calbindin-D28k and ionized calcium without increasing intestinal calb indin-D9k. The effect of the high calcemic vitamin D analogs KH1060 an d GS1725 on calbindin-D was directly related to their calcemic activit y. In conclusion, these results demonstrate that 24,25-(OH)(2)D-3 incr eases intestinal calbindin-D9k, but has no effect on renal calbindin-D 28k, that low calcemic analogs may increase renal calbindin-D28k witho ut increasing intestinal calbindin-D9k, and that the effect of high ca lcemic analogs on calbindin-D is directly related to their calcemic ac tivity.