Attenuated up-regulation of vitamin D-dependent calcium-binding proteins by 22-oxa-1,25-dihydroxyvitamin D3 in uremic rats:: A possible mechanism for less-calcemic action

被引:7
作者
Ichikawa, F
Hirata, M
Endo, K
Katsumata, K
Ohkawa, H
Kubodera, N
Fukagawa, M
Kurokawa, K
机构
[1] Tokyo Teishin Hosp, Div Nephrol, Chiyoda Ku, Tokyo 1028798, Japan
[2] Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka, Japan
[3] Univ Tokyo, Sch Med, Tokyo 113, Japan
[4] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan
关键词
calcium binding protein; chronic renal failure; parathyroid hormone; secondary hyperparathyroidism; 22-oxa-1,25D3; vitamin D;
D O I
10.1111/j.1440-1797.1998.tb00377.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
22-Oxa-1,25-dihydroxyvitamin D-3 (OCT) is an analogue of vitamin D with less calcemic action than 1,25 dihydroxyvitamin D, (1,25D3), and thus may be advantageous in the treatment of secondary hyperparathyroidism in dialysis patients. To further elucidate the mechanisms of less-calcemic action of OCT in chronic renal failure, we examined the effects of OCT and 1,25D3 on mRNA levels for vitamin D-dependent 9-KDa calcium binding protein (CaBP-D-9K) in the intestinal mucosa and 28-KDa (CaBP-D-28K) in the kidney. In Sprague-Dawley rats made uremic by 5/6 nephrectomy for three months, OCT at doses of 0.25, 1.25 and 6.25 mu g/kg, or 1,25D3 at 0.025, 0.125 and 0.625 mu g/kg were administered intravenously three times per week for two weeks. At 24 h after the final injection, enhanced serum PTH and PTH mRNA levels were successfully suppressed both by OCT and 1,25D3 in a dose dependent manner. However, OCT induced less hypercalcemia than 1,25D3. 1,25D3 markedly upregulated the expression of CaBP-D-9K, and CaBP-D-28K genes, while they were not affected by OCT at all. In conclusion, such attenuated effects of OCT on calcium-binding proteins may play a role in the noncalcemic action, because number of CaBP-D-9K has been suggested to correlate with calcium absorption in the intestine.
引用
收藏
页码:391 / 395
页数:5
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