Enterohepatic physiology of 1,25-dihydroxyvitamin D3.
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.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D004764:Enterohepatic Circulation; D005966:Glucuronidase / Q000494:pharmacology; D006887:Hydroxycholecalciferols / Q000378:metabolism*; D008297:Male; D051381:Rats; D013997:Time Factors
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D005966:Glucuronidase