Regulation of 24-hydroxylase activity in mouse skin fibroblast by cholecalciferol derivatives, triamcinolone acetonide and a calcium modulating agent, nicardipine.
Mouse skin fibroblasts in culture were used to study the regulation of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) induced 24 hydroxylase (24-OH-ase) under the influence of 3 agents: (1) 24,25-Dihydroxycholecalciferol (24,25(OH)2D3), 62.5 10(-9) M, which led to a significant decrease in the 1,25(OH)2D3-induced 24-OH-ase, probably acted through a nuclear effect mediated by the 1,25(OH)2D3 receptor protein. (2) Triamcinolone acetonide (10(-6)M) which was found to increase the 24-OH-ase enhancement induced by 1.25 and 6.25 nM 1,25(OH)2D3 whereas it did not alter the effect of 31.2 nM 1,25(OH)2D3. (3) A factor which is likely to induce changes in the cell calcium transport or in the Ca pool sizes, i.e. a calcium channel blocker, nicardipine. The effect of 1.25 nM 1,25(OH)2D3 on 24-OH-ase activity was increased by nicardipine (20 microM) which was found to reduce the effect of 6.25 nM 1,25(OH)2D3. The rate of DNA synthesis (measured by [3H]thymidine incorporation) was increased after incubation of fibroblasts with 1,25(OH)2D3 (1.25 nM) plus triamcinolone acetonide (10(-6) M), although it was reduced by nicardipine in comparison with 1,25(OH)2D3 alone. So the effects of these agents on the 1,25(OH)2D3 induced 24-hydroxylase were shown to be independent of the rate of DNA synthesis.
Cancela
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L
U 18 INSERM, Paris, France.
Rebut-Bonneton
C
C
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009529:Nicardipine / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase
D004100:Dihydroxycholecalciferols; C031699:23,25-dihydroxyvitamin D3; D003577:Cytochrome P-450 Enzyme System; D009529:Nicardipine; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D014222:Triamcinolone Acetonide; D002117:Calcitriol