22-oxacalcitriol suppresses 25-hydroxycholecalciferol-1 alpha-hydroxylase in rat kidney.
22-oxacalcitriol can decrease the serum level of 1,25-dihydroxycholecalciferol by increasing its metabolic clearance rate and decreasing its production rate. To determine whether 22-oxacalcitriol suppressed the renal 25-hydroxycholecalciferol-1 alpha- hydroxylase we treated rats with 200 ng of 22-oxacalcitriol daily for 1 week. Enzyme activity was measured in vitro by measurement of production of 1,25-dihydroxycholecalciferol by renal slices incubated with 25-hydroxycholecalciferol. 22-oxacalcitriol significantly decreased the 25-hydroxycholecalciferol-1 alpha-hydroxylase activity from 797 +/- 208 pg of 1,25-dihydroxycholecalciferol/g of kidney/h in the control group to 257 +/- 150 pg of 1,25-dihydroxycholecalciferol/g of kidney/h (p less than 0.05). This is the first demonstration of suppression of the renal 25-hydroxycholecalciferol-1 alpha-hydroxylase by the vitamin D3 analog, 22-oxacalcitriol.
Grieff
M
M
Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110.
Dusso
A
A
Mori
T
T
Nishii
Y
Y
Slatopolsky
E
E
Brown
A J
AJ
D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; C051883:maxacalcitol; D002112:Calcifediol; D002118:Calcium