Abstract
The response of intestinal calcium-binding protein (CaBP) synthesis and the rise in the serum calcium level to vitamin D metabolites were measured in vitamin D-deficient rats fed a low-calcium diet. Our results showed a linear relationship between the amount of intestinal CaBP and the logarithm of the dose for all the compounds. 1,24(R),25-(OH)3D3 was approximately four times less effective than 1,25-(OH)2D3 in increasing the CaBP level and about eight times more effective than 24(R),25-(OH)2D3. The bone calcium mobilization response expressed as the rise in serum calcium was also dose related. The relative potencies of the metabolites in increasing the serum calcium level were approximately the same as those elevating CaBP synthesis. Time course studies showed that 1,24(R),25-(OH)3D3 was as rapidly active as 1,25-(OH)2D3 in inducing intestinal CaBP synthesis and increasing serum calcium. The duration of its calcemic response was shorter and the magnitude less than that of 1,25-(OH)2D3. A longer time lag was necessary to obtain intestinal and calcemic responses after 24(R),25-(OH)2D3 injection. 1,24(R),25-(OH)3D3 and 1,25-(OH)2D3 were still active in promoting intestinal CaBP synthesis in nephrectomized rats, whereas a large dose of 24(R),25-(OH)2D3 was inactive. Thus C-1 hydroxylation is essential for the stimulation of both the intestinal CaBP production and the rise in the serum calcium level, whereas C-24 hydroxylation diminishes the magnitude of the intestinal and calcemic responses. These results strongly suggest that 1,24(R),25-(OH)3D3 represents an inactivation rather than an activation of the hormonal form of vitamin D3.
ACKNOWLEDGMENTS We are grateful to N. Gouhier and A. Subrenat for expert and devoted technical assistance and to M. Courat and P. Schuman for the preparation of the manuscript. We wish to thank Dr. P. Marche for supplying CaBP-specific antiserum and Dr. M. Moukhtar (INSERM U. 113, Paris) for providing us with laboratory facilities to prepare 125I-CaBP). We are grateful to Dr. Uskokovic (Hoffmann-La Roche, Nutley, New Jersey) for supplying the synthetic compounds.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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