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

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 μM) 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 bileflow, a significant increase in taurocholate apparent choleretic activity (13.2 μl/μmol vs 10.6 μl/μmol; p=0.05), while taurocholate intrinsic clearance was significantly decreased (4.5±1.2 ml • min−1 • g−1 vs 6.1±1.3 ml• min−1 • 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.