Effects of amino acids on bile acid-dependent and independent bile flow inthe 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 p erfused rat liver model. Methods: To investigate the influence of amino acids on the bile acid-indep endent component of bile flow, 12 livers were perfused with (n=6) and witho ut (n=6) amino acid addition from t30 min. For the study of bile acid-depen dent bile flow, 24 livers were perfused under 8 experimental conditions acc ording to the perfusate taurocholate concentration (12.5, 25, 37.5 or 50 mu M) 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 increa se in bile flow. When livers were perfused at various taurocholate concentr ations, 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 mu l/mu mol vs 10.6 mu l/mu mol; 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 concentrati ons 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 m echanisms.