Abstract
The prior administration of actinomycin D prevents the metabolism of [3H]25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol, a metabolite of vitamin D3 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.
Keywords: rat, vitamin D, actinomycin D, kidney, “peak V” metabolite
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- Blunt J. W., DeLuca H. F., Schnoes H. K. 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry. 1968 Oct;7(10):3317–3322. doi: 10.1021/bi00850a001. [DOI] [PubMed] [Google Scholar]
- Blunt J. W., DeLuca H. F. The synthesis of 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry. 1969 Feb;8(2):671–675. doi: 10.1021/bi00830a031. [DOI] [PubMed] [Google Scholar]
- Cousins R. J., DeLuca H. F., Chen T., Suda T., Tanaka Y. Metabolism and subcellular location of 25-hydroxycholecalciferol in intestinal mucosa. Biochemistry. 1970 Mar 17;9(6):1453–1459. doi: 10.1021/bi00808a021. [DOI] [PubMed] [Google Scholar]
- Cousins R. J., DeLuca H. F., Gray R. W. Metaboism of 25-hydroxycholecalciferol in target and nontarget tissues. Biochemistry. 1970 Sep 15;9(19):3649–3652. doi: 10.1021/bi00821a001. [DOI] [PubMed] [Google Scholar]
- DeLuca H. F. Recent advances in the metabolism and function of vitamin D. Fed Proc. 1969 Sep-Oct;28(5):1678–1689. [PubMed] [Google Scholar]
- Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
- Haussler M. R., Boyce D. W., Littledike E. T., Rasmussen H. A rapidly acting metabolite of vitamin D3. Proc Natl Acad Sci U S A. 1971 Jan;68(1):177–181. doi: 10.1073/pnas.68.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haussler M. R., Myrtle J. F., Norman A. W. The association of a metabolite of vitamin D3 with intestinal mucosa chromatin in vivo. J Biol Chem. 1968 Aug 10;243(15):4055–4064. [PubMed] [Google Scholar]
- Holick M. F., Schnoes H. K., DeLuca H. F. Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci U S A. 1971 Apr;68(4):803–804. doi: 10.1073/pnas.68.4.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kodicek E., Lawson D. E., Wilson P. W. Biological activity of a polar metabolite of vitamin D. Nature. 1970 Nov 21;228(5273):763–764. doi: 10.1038/228763a0. [DOI] [PubMed] [Google Scholar]
- Lawson D. E., Fraser D. R., Kodicek E., Morris H. R., Williams D. H. Identification of 1,25-dihydroxycholecalciferol, a new kidney hormone controlling calcium metabolism. Nature. 1971 Mar 26;230(5291):228–230. doi: 10.1038/230228a0. [DOI] [PubMed] [Google Scholar]
- Lawson D. E., Wilson P. W., Kodicek E. Metabolism of vitamin D. A new cholecalciferol metabolite, involving loss of hydrogen at C-1, in chick intestinal nuclei. Biochem J. 1969 Nov;115(2):269–277. doi: 10.1042/bj1150269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lund J., DeLuca H. F. Biologically active metabolite of vitamin D3 from bone, liver, and blood serum. J Lipid Res. 1966 Nov;7(6):739–744. [PubMed] [Google Scholar]
- Martin D. L., DeLuca H. F. Influence of sodium on calcium transport by the rat small intestine. Am J Physiol. 1969 Jun;216(6):1351–1359. doi: 10.1152/ajplegacy.1969.216.6.1351. [DOI] [PubMed] [Google Scholar]
- Myrtle J. F., Haussler M. R., Norman A. W. Evidence for the biologically active form of cholecalciferol in the intestine. J Biol Chem. 1970 Mar 10;245(5):1190–1196. [PubMed] [Google Scholar]
- Myrtle J. F., Norman A. W. Vitamin D: A cholecalciferol metabolite highly active in promoting intestinal calcium transport. Science. 1971 Jan 8;171(3966):79–82. doi: 10.1126/science.171.3966.79. [DOI] [PubMed] [Google Scholar]
- Neville P. F., DeLuca H. F. The synthesis of [1,2-3H]vitamin D3 and the tissue localization of a 0.25-mu-g (10 IU) dose per rat. Biochemistry. 1966 Jul;5(7):2201–2207. doi: 10.1021/bi00871a007. [DOI] [PubMed] [Google Scholar]
- Norman A. W. Vitamin D mediated synthesis of rapidly labeled RNA from intestinal mucosa. Biochem Biophys Res Commun. 1966 May 3;23(3):335–340. doi: 10.1016/0006-291x(66)90551-1. [DOI] [PubMed] [Google Scholar]
- Ponchon G., Deluca H. F. Metabolites of vitamin D3 and their biologic activity. J Nutr. 1969 Oct;99(2):157–167. doi: 10.1093/jn/99.2.157. [DOI] [PubMed] [Google Scholar]
- Stohs S. J., Zull J. E., DeLuca H. F. Vitamin D stimulation of [3H]orotic acid incorporation into ribonucleic acid of rat intestinal mucosa. Biochemistry. 1967 May;6(5):1304–1310. doi: 10.1021/bi00857a012. [DOI] [PubMed] [Google Scholar]
- Suda T., DeLuca H. F., Tanaka Y. Biological activity of 25-hydroxyergocalciferol in rats. J Nutr. 1970 Sep;100(9):1049–1052. doi: 10.1093/jn/100.9.1049. [DOI] [PubMed] [Google Scholar]
- Tanaka Y., DeLuca H. F. Inhibition of the metabolism of 25-hydroxycholecalciferol by actinomycin D and cycloheximide. Proc Natl Acad Sci U S A. 1971 Mar;68(3):605–608. doi: 10.1073/pnas.68.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zull J. E., Czarnowska-Misztal E., DeLuca H. F. On the relationship between vitamin D action and actinomycin-sensitive processes. Proc Natl Acad Sci U S A. 1966 Jan;55(1):177–184. doi: 10.1073/pnas.55.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zull J. E., Czarnowska-Misztal E., Deluca H. F. Actinomycin D Inhibition of Vitamin D Action. Science. 1965 Jul 9;149(3680):182–184. doi: 10.1126/science.149.3680.182. [DOI] [PubMed] [Google Scholar]