Effects of amino acids on bile acid-dependent and independent bile flow in the isolated perfused rat liver

J Hepatol. 1999 May;30(5):843-9. doi: 10.1016/s0168-8278(99)80138-x.

Abstract

Background/aims: Conflicting data on the effects of amino acids on biliary function led us to investigate their interaction with taurocholate in the perfused rat liver model.

Methods: To investigate the influence of amino acids on the bile acid-independent component of bile flow, 12 livers were perfused with (n = 6) and without (n = 6) amino acid addition from t30 min. For the study of bile acid-dependent bile flow, 24 livers were perfused under 8 experimental conditions according to the perfusate taurocholate concentration (12.5, 25, 37.5 or 50 microM) and whether amino acids were or were not added from t30 min.

Results: In the absence of taurocholate, amino acids induced a 40% (p<0.01) decrease in bile flow together with an increase in hepatic water content (17.8%, p< 0.05). Thus, amino acids exert an inhibitory effect on bile acid-independent bile flow despite the postulated cell swelling-dependent increase in bile flow. When livers were perfused at various taurocholate concentrations, amino acids induced, in addition to their inhibitory effect on bile acid-independent bile flow, a significant increase in taurocholate apparent choleretic activity (13.2 microl/micromol vs. 10.6 microl/micromol; p = 0.05), while taurocholate intrinsic clearance was significantly decreased (4.5+/-1.2 ml x min(-1) x g(-1) vs. 6.1+/-1.3 ml x min(-1) x g(-1); p<0.01).

Conclusions: These data suggest that at physiological bile acid concentrations amino acids exert an inhibitory effect on both bile acid-dependent and- independent bile flow, whereas at higher taurocholate concentrations this inhibitory effect disappears, probably because of cell swelling-dependent mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology*
  • Animals
  • Bile / drug effects
  • Bile / metabolism*
  • Bile Acids and Salts / pharmacology*
  • Body Water / metabolism
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Kinetics
  • Liver / drug effects
  • Liver / physiology*
  • Male
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Taurocholic Acid / pharmacology*

Substances

  • Amino Acids
  • Bile Acids and Salts
  • Taurocholic Acid