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标题：Metabolism of [3α-3H] 25-Hydroxyvitamin D2 in Kidneys Isolated from Normal and Vitamin D2-intoxicated Rats
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作者：Devara SUNITA RAO ; Rahul RAY ; Michael F. HOLICK 等
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2000
卷号：46
期号：5
页码：222-229
DOI：10.3177/jnsv.46.222
出版社：Center for Academic Publications Japan
摘要：With the availability of A-ring labelled 25OHD₂, [3α-³H] 25OHD₂, we have performed the present study to examine the metabolism of 25OHD₂ using physiological substrate concentrations in perfused kidneys isolated from both normal and vitamin D₂-intoxi-cated rats. Our results indicate that [3α-³H] 25OHD₂ is metabolized into both 24(S), 25, 28-trihydroxyvitamin D₂ [24(S), 25, 28(OH)₃D₂] and 24(R), 25, 26-trihydroxyvitamin D₂ [24(R), 25, 26(OH)₃D₂], and the amounts of these two metabolites produced in the kidney of vitamin D₂-intoxicated rat were about 3-5 times higher than those produced in the kidney of normal rat. Similar results were also obtained with rat kidney homogenates incubated with [3a-3H] 250HD2. Furthermore, we noted that the production of both 24(S), 25, 28(OH)₃D₂ and 24(R), 25, 26(OH)₃D₂ in the kidney homogenates of vitamin D₂-intoxicated rats increased with the time of incubation and then subsequently decreased. The decrease in both 24(5), 25, 28(OH)₃D₂ and 24(R), 25, 26(OH)₃D₂ coincided with an increase in the fraction of total radioactivity distributed in the aqueous phase of the kidney homogenates. This finding suggested the possibility of further metabolism of 24(S), 25, 28(OH)₃D₂ and 24(R), 25, 26(OH)₃D₂ into polar water-soluble metabolite(s). We then measured the radioactivity in the aqueous phase of kidney homogenates of both normal and vitamin D₂-intoxicated rats incubated with [3α-³H]25OHD₂. It was noted that the amount of radioactivity in the aqueous phase of kidney homogenates of vitamin D₂-intoxicated rats is higher than that present in the aqueous phase of kidney homogenates of normal rats. Thus, our study provides evi-dence for the first time for the formation of both 24(S), 25, 28(OH)₃D₂ and 24(R), 25, 26(OH)₃D₂ under physiological conditions, and the possibility of their further metabolism into as yet unidentified polar water-soluble metabolite(s). As the formation of all these metabolites is increased in the kidney of vitamin D2-intoxicated rats when compared to normal rats, it appears that the increased rate of metabolism of 25OHD₂ during hypervitaminosis D₂ plays a significant role in the deactivation of 25OHD₂.
关键词：polar water-soluble metabolite(s);hydroxylation;kidney;metabolism;vitamin D2-intoxicated rats;25OHD2