METABOLISM OF 22-OXACALCITRIOL BY A VITAMIN-D-INDUCIBLE PATHWAY IN CULTURED PARATHYROID CELLS

被引:23
作者
BROWN, AJ [1 ]
BERKOBEN, M [1 ]
RITTER, C [1 ]
KUBODERA, N [1 ]
NISHII, Y [1 ]
SLATOPOLSKY, E [1 ]
机构
[1] CHUGAI PHARMACEUT LTD,TOKYO,JAPAN
关键词
D O I
10.1016/0006-291X(92)92266-Z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Catabolism of 22-oxacalcitriol (OCT) in parathyroid cells was compared to that of the parent hormone, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Catabolism of both compounds was greatly accelerated by pretreatment of the cells with 1,25-(OH)2D3 or OCT. The rate of degradation of OCT was slightly greater than that of 1,25-(OH)2D3. Excess unlabeled OCT or 1,25-(OH)2D3 inhibited metabolism of both tritiated substrates. Ketoconazole, a cytochrome P450 inhibitor, blocked catabolism of both compounds. The major OCT metabolite appeared to be 1,20-dihydroxy-22,23,24,25,26,27-hexanor-vitamin D3 which was not active in suppressing PTH secretion. We conclude that OCT appears to be metabolized by the same vitamin D-inducible side chain oxidation pathway that catabolizes other vitamin D compounds and that its higher than expected suppression of PTH secretion is not due to slower cellular metabolism. © 1992.
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页码:759 / 764
页数:6
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