Bile acid structure and bile formation in the guinea pig

Abstract

The effects of intravenous infusions (1-4 mumol/min/kg) of 14 bile acids, cholic, deoxycholic, ursodeoxycholic, chenodeoxycholic, dehydrocholic, and their glycine and taurine conjugates, on bile flow and composition and on the biliary permeation of inert carbohydrates have been studied in the guinea pig bile fistula. Hydroxy bile acids were eliminated in bile without major transformation, except for conjugation (over 90%) when unconjugated bile acids were infused. During infusion of dehydrocholate and taurodehydrocholate, 77-100% of the administered dose was recovered in bile as 3-hydroxy bile acids, thus indicating that reduction of the keto group in position 3 was virtually complete. All bile acids produced choleresis at the doses employed: the strongest choleretic was deoxycholate (81.78 microliters/mumol), the weakest was taurodehydrocholate (10.2 microliters/mumol). Choleretic activity was directly and linearly related to bile acid hydrophobicity, as inferred by HPLC, both for similarly conjugated bile acids, and for bile acids having the same number, position, or configuration of the hydroxyl groups. In all instances, the rank ordering was: deoxycholate greater than chenodeoxycholate greater than cholate greater than ursodeoxycholate. During choleresis produced by any of the bile acids tested, bicarbonate concentration in bile slightly declined, but the calculated concentration in bile-acid-stimulated bile (45-57 mmol/l) was always higher than that measured in plasma (23-26 mmol/l). Biliary concentrations of cholesterol (20-68 mumol/l) and phospholipid (14-63 mumol/l) were very low during spontaneous secretion, and declined even further following bile acid choleresis. None of the infused bile acids consistently modified biliary excretion of cholesterol and phospholipid. Consistent with a previous observation from this laboratory, all hydroxy bile acids reversibly diminished [14C]erythritol and [14C]mannitol biliary entry during choleresis, while they increased or failed to modify that of [3H]sucrose and [3H]inulin. The rank ordering for the inhibitory effect on [14C]erythritol and [14C]mannitol permeation was: 3 alpha,7 alpha,12 alpha-trihydroxy greater than 3 alpha,7 alpha-dihydroxy greater than 3 alpha,7 beta-dihydroxy greater than 3 alpha,12 alpha-dihydroxy bile acids.(ABSTRACT TRUNCATED AT 400 WORDS)