Heterogeneity of rat liver parenchyma in taurocholate uptake

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar distribution of taurocholate uptake. Statistical analysis revealed that uptake of taurocholate by periportal, perivenous and regular (whole acinus) hepatocytes in Na+-containing and -free buffer was best described by one saturable component. Total taurocholate uptake measured in Na+-containing buffer was significantly higher in perivenous (V-max = 7.5 nmol/(min mg protein)) than in periportal hepatocytes (V-max =5.4 nmol/(min mg protein)). Uptake by regular hepatocytes was well between the values of periportal and perivenous hepatocytes (V-max = 6.7 nmol/(min mg protein)). The K-m-values were not different among the zonal regions. In Na+-free buffer, K-m and V-max of taurocholate uptake calculated for all fractions were similar. During cultivation of hepatocytes as monolayer total taurocholate uptake strongly decreased and the zonal differences observed in freshly isolated cells in suspension disappeared. Initial uptake rates of Na+-independent taurocholate uptake and the ATP-content of the hepatocytes were constant. Our results indicate an acinar gradient of Na+-dependent taurocholate uptake activity, which may improve the clearance of bile salts from portal blood and protect periportal hepatocytes against a too high intracellular bile salt concentration. (C) 2003 Elsevier B.V. All rights reserved.