Metabolism of 22-oxacalcitriol by a vitamin D-inducible pathway in cultured parathyroid cells.
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.
Brown
A J
AJ
Renal Division, Washington University School of Medicine, St. Louis, MO 63110.
Berkoben
M
M
Ritter
C
C
Kubodera
N
N
Nishii
Y
Y
Slatopolsky
E
E
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*
D002117:Calcitriol; C051883:maxacalcitol