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

SUMMARY: 22‐Oxa‐1,25‐dihydroxyvitamin D3 (OCT) is an analogue of vitamin D with less calcemic action than 1,25‐dihydroxyvitamin D3 (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‐D9K) in the intestinal mucosa and 28‐KDa (CaBP‐D28K) 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 μg/kg, or 1,25D3 at 0.025,0.125 and 0.625 μg/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‐D9K and CaBP‐D28K 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‐D9K has been suggested to correlate with calcium absorption in the intestine.

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