Hepatic transport of bile acids in the isolated perfused rat liver. Structure-kinetic relationship

We studied the transport kinetics of a series of bile acids from blood to bile in the isolated perfused rat liver in order to define better the relationship between chemical structure of bile acid molecules and efficiency of the overall hepatic transport process. BA studied were taurocholate (TC), glycocholate (GC), cholate (C), tauroursodeoxycholate (TUDC), ursodeoxycholate (UDC) and hyodeoxycholate (HDC). Estimates of intrinsic hepatic clearance (Cl(int)), maximal secretory rate (Vmax) were provided from the analysis of the relationship between bile acid removal rates and sinusoidal concentration under steady-state conditions. TC and TUDC had the highest Cl(int) (about 5 ml/min/g liver) and Vmax (about 800 nmol/min/g liver) followed in order by GC (1.71 ml/min/g liver; 442 nmol/min/g liver); C (1.25 ml/min/g liver; 252 nmol/min/g liver); HDC (0.86 ml/min/g liver; 238 nmol/min/g liver); UDC (0.72 ml/min/g liver; 176 nmol/min/g liver). The findings suggest that the efficiency of the overall hepatic transport of bile acids is highly dependent on their molecular structure and that conjugation has a more important effect on both Cl(int) and Vmax that the number or position of hydroxyl groups.