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

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.