Kumar R, Nagubandi S, Mattox V R, Londowski J M
J Clin Invest. 1980 Feb;65(2):277-84. doi: 10.1172/JCI109669.
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.
给大鼠静脉注射放射性标记的1,25 - 二羟基维生素D3后，在24小时内约25%的注入放射性出现在胆汁中。将胆汁中的放射性物质注入其他大鼠的十二指肠后，24小时内新分泌的胆汁中回收了15%的放射性物质。在测试剂量范围（0.275 - 650纳克）内，1,25 - 二羟基维生素D3产物经胆汁排泄的过程不饱和。发现胆汁中存在的1,25 - 二羟基维生素D3代谢产物比1,25 - 二羟基维生素D3极性大得多，在高效液相色谱上可分离为三个组分。胆汁中60%的放射性物质被DEAE - 纤维素选择性保留；放射性物质可在低pH值或高盐浓度下从凝胶上洗脱下来。当含有放射性标记代谢产物的胆汁在37℃和pH 5条件下与β - 葡萄糖醛酸酶一起孵育时，与1,25 - 二羟基维生素D3共迁移的放射性物质数量增加。用重氮甲烷（一种将酸转化为甲酯的试剂）处理胆汁中放射性标记的1,25 - 二羟基维生素D3产物，可将其中一种代谢产物转化为极性较小的化合物。这些结果表明，在大鼠中1,25 - 二羟基维生素D3产物存在数量上重要的肠肝循环。
