Mechanism of action of 1,25-dihydroxycholecalciferol on intestinal calcium transport.

The prior administration of actinomycin D prevents the metabolism of [(3)H]25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol, a metabolite of vitamin D(3) that is effective in the stimulation of intestinal calcium transport. In this paper, the question of whether the response of intestinal calcium transport to 1,25-dihydroxycholecalciferol is sensitive to actinomycin D was examined. While the response of intestinal transport to physiological amounts of 25-hydroxycholecalciferol is blocked by actinomycin D, the response of intestinal calcium transport to 1,25-dihydroxycholecalciferol is insensitive to the antibiotic. These results suggest that 1,25-dihydroxycholecalciferol, or a further metabolite thereof, is the metabolically active form of vitamin D in the intestine, that it functions by a process not involving transcription of DNA, and that the step sensitive to actinomycin D in the action of vitamin D on the intestine does not occur in the intestine, but is the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney.