Production in vitro of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone from 1 alpha,25-dihydroxyvitamin D2 by rat small intestinal mucosa homogenates |
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Authors: | N Ohnuma A W Norman |
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Affiliation: | 1. Department of Biochemistry, University of California, Riverside, California 92521 USA;2. Teijin Institute for Bio-medical Research, 4-3-2, Asahigaoka, Hino Tokyo 191, Japan |
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Abstract: | The metabolism of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] in the rat has been studied under both in vivo and in vitro conditions. A time course study of the appearance of 1α,25-dihydroxyvitamin D3-26,23-lactone in the plasma following intravenous or oral administration of 1α,25(OH)2D3 suggests that the small intestine may take part in production of the 1α,25(OH)2D3-26,23-lactone. In an in vitro study using a homogenate of rat small intestinal mucosa, 1α,25(OH)2D3 undergoes further metabolism to give more polar metabolite(s) which comigrate with authentic 1α,24,25-trihydroxyvitamin D3 [1α,24,25(OH)3D3] on Sephadex LH-20 column chromatography. The metabolic profile obtained after high-pressure liquid chromatography reveals two major classes of metabolites, designated Peaks X and Y. Peak X is an unidentified metabolite of 1α,25(OH)2D3. Peak Y is chromatographically identical with 1α,25-dihydroxyvitamin D3-26,23-lactone which has been recently isolated from the plasma of rats and dogs as a major metabolite produced in vivo from either 1α,25(OH)2D3 or 1α-hydroxyvitamin D3 (N. Ohnuma, K. Bannai, H. Yamaguchi, Y. Hashimoto, and A. W. Norman, 1980, Arch. Biochem. Biophys.204, 387). The enzyme activity which produces metabolites X and Y in the rat intestinal homogenates is induced in vitamin D-replete rats by pretreatment of the animals with intravenous 1.25 μg/kg doses of 1α,25-dihydroxyvitamin D3, 6 to 8 h previously. |
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