The hepatic transport of five bile acids was studied in the bile-fistula rat. Pairs of labeled bile acids were injected simultaneously into the portal vein as a sharp pulse and the secretion of radiolabel in bile was measured over the nex 15 min. Six bile acid pairs were tested, and it was found that both conjugation and the number and disposition of hydroxyl groups influenced hepatic transport. Taurocholic acid was transported most efficiently, followed in order by glycocholic acid, cholic acid, deoxycholic acid, and chenodeoxycholic acid. Sampling aortic blood immediately after portal vein injection of labeled bile acid pairs demonstrated differential rates of hepatic extraction. In every comparison, the bile acid that was more efficiently extracted by the liver had a faster overall transport rate. This suggests that the differing rates of biliary secretion are, at least in part, determined by the efficiency of hepatic uptake.
An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.
2H-glycine-1-2C was administered orally to eight healthy subjects with indwelling nasoduodenal tubes. The distribution of radioactivity among bile acids and the specific activity of cholylglycine were determined in bile collected at intervals for 7 days. 8H and "C were measured in stool. "C in breath was calculated from interval "CO2 specific activity determinations.The daily fractional turnover of the glycine moiety (mean +SE, 106±17%) was three times greater than that of the cholyl moiety (38±7%). On the basis of certain assumptions, it was calculated that about 18% of the cholylglycine pool was deconjugated per enterohepatic cycle. The extent of deconjugation appeared to be unrelated to the efficiency of absorption of the cholyl moiety, which averaged 90-95% per enterohepatic cycle. "C was recovered predominantly in breath (52±5% of administered dose), and 24 hr 'CO2 excretion correlated highly (r = 0.95) with daily fractional turnover of the glycine moiety. 'H excretion occurred predominantly in feces, and the rate correlated highly (r = 0.92) with the daily fractional turnover of the cholyl moiety. Deoxycholylglycine became labeled with 'H rapidly, indicating the occurrence of bacterial 7-dehydroxylation of the cholyl moiety and absorption of deoxycholic acid. This biotransformation occurred in all eight subjects but varied in degree and was unrelated to the degree of deconjugation. Since ingested glycine-1-2C was not incorporated into bile acid glycine, appearance of "C in deoxycholylglycine (observed in three of eight subjects) indicated that 7-dehydroxylation of cholylglycine can occur without deconjugation. Dehydroxylation was also observed in vitro when fecal homogenates were incubated with cholylglycine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.