Ileal absorption of tyrosine-conjugated bile acids in Wistar rats.
We recently reported that tyrosine-conjugated bile acids, when injected intravenously into bile-fistula rats, are extracted by the liver and secreted intact into bile with an efficiency similar to that seen for taurocholate. Now the effect of tyrosine and glycyltyrosine conjugation of bile acids on ileal absorption has been studied in Wistar rats. 125I-labelled tyrosine- and glycyltyrosine-conjugated bile acid or [14C]taurocholate was injected in 400 microliters aliquots of physiological saline buffered to pH 7.8 into the ileal lumen of bile-fistula rats. Recovery of bile salts in bile was taken as proof of ileal absorption. In comparison with taurocholate, ileal absorption was about 10% less for cholyltyrosine and chenodeoxycholyltyrosine and about 50% less for deoxycholyltyrosine. Thus, tyrosine-conjugated bile acids are absorbed by the ileum and excreted into bile and may undergo enterohepatic circulation. Low recoveries of deoxycholyltyrosine relative to deoxycholylglycine suggested that side chain structure was important for ileal absorption of 3 alpha,12 alpha-dihydroxy bile acids. Elongation of cholic acid to form cholylglycyltyrosine markedly reduced 90-min cumulative ileal absorption relative to cholyltyrosine. Although initial rates of recovery of cholylglycyltyrosine were comparable to those of the other bile acids, very little further absorption was seen in the last hour of the experiment, suggesting that this compound was rapidly degraded within the intestinal lumen.
Mills
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Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
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Elias
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D000818:Animals; D001647:Bile Acids and Salts / Q000493:pharmacokinetics*; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D019826:Cholic Acid; D002793:Cholic Acids / Q000493:pharmacokinetics; D003840:Deoxycholic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004151:Dipeptides / Q000493:pharmacokinetics; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D014443:Tyrosine / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D002793:Cholic Acids; D004151:Dipeptides; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; C054057:chenodeoxycholyltyrosine; C054058:deoxycholyltyrosine; D014443:Tyrosine; D013656:Taurocholic Acid; C022013:glycyltyrosine; D019826:Cholic Acid