Enterohepatic physiology of 1,25-dihydroxyvitamin D3.

Enterohepatic physiology of 1,25-dihydroxyvitamin D3.
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1,25-二羟基维生素 D3 的肠肝生理学。

DOI:
10.1172/jci109669
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发表时间:
1980
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Londowski,JM
Londowski,JM
中科院分区:
--
文献类型:
--
作者:
Kumar,R;Nagubandi,S;Mattox,VR;Londowski,JM

文献摘要

被引文献

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大鼠静脉注射放射性标记的1,25-二羟基维生素D3后,约25%的放射性在24小时内出现在胆汁中,其他大鼠十二指肠注射后,新分泌的胆汁中15%的放射性在24小时内恢复,1,25-二羟基维生素D3产物在胆汁中的排泄过程在所测剂量范围内(0.275-650 ng)是不饱和的。胆汁中存在的1,25-二羟基维生素D3的代谢产物比1,25-二羟基维生素D3的极性更强,并在高效液相色谱法上被分解成三个组分。胆汁中60%的放射性被DEAE-纤维素选择性地保留;在低pH或高盐浓度下,放射性物质可以从凝胶中洗脱。当含有放射性标记代谢物的胆汁在37℃和pH为5的条件下与β-葡萄糖苷酸酶孵育时,1,25-二羟基维生素D3的放射性迁移量增加。胆汁中放射性标记的1,25-二羟基维生素D3产物用重氮甲烷处理,重氮甲烷是一种将酸转化为甲酯的试剂,将其中一种代谢物转化为低极性化合物。这些结果表明,1,25-二羟基维生素D3的产物在大鼠体内存在数量上重要的肠-肝循环。
After intravenous administration of radiolabeled 1,25-dihydroxyvitamin D3 to rats, approximately 25% of the administered radioactivity appeared in the bile within 24 h. Instillation of the biliary radioactivity into the duodena of other rats was followed by recovery of 15% of the radioactivity in newly secreted bile within 24 h. The process by which products of 1,25-dihydroxyvitamin D3 were excreted in bile was not saturable in the dose range tested (0.275-650 ng). The metabolites of 1,25-dihydroxyvitamin D3 present in bile were found to be much more polar than 1,25-dihydroxyvitamin D3 and were resolved into three fractions on high performance liquid chromatography. 60% of the radioactivity present in bile was retained selectively by DEAE-cellulose; the radioactive material could be eluted from the gel at a low pH or at high salt concentrations. When bile containing the radiolabeled metabolites was incubated at 37 degrees C and pH 5 with beta-glucuronidase, there was an increase in the amount of radioactivity comigrating with 1,25-dihydroxyvitamin D3. Treatment of the products of radiolabeled 1,25-dihydroxyvitamin D3 in bile with diazomethane, an agent which converts acids into methyl esters, transformed one of the metabolites into a less polar compound. These results demonstrate that there is a quantitatively important enterophepatic circulation of the products of 1,25-dihydroxyvitamin D3 in the rat.