Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3.
Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D002762:Cholecalciferol / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014316:Tritium; D014807:Vitamin D / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism*
D004100:Dihydroxycholecalciferols; D014316:Tritium; D014807:Vitamin D; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3