Absence of an acinar gradient for bile acid uptake in developing rat liver

We studied the acinar distribution for uptake of the bile acid analogue [125I]-cholylglycyltyrosine in livers from adult and 14-day-old suckling rats. Portal and peripheral (systemic) serum bile acid concentrations were also measured by combined gas chromatography-mass spectrometry as an independent index of hepatic bile acid clearance from portal blood. Utilizing light microscopic autoradiography, a steep, decreasing portal to centrilobular gradient for cholylglycyltyrosine uptake was noted in adult rat liver. In contrast, there was no lobular gradient for cholylglycyltyrosine uptake visible in the 14-day-rat liver; all hepatocytes within the acinus contained a similar number of silver grains. Portal vein total bile acid concentrations were significantly higher in serum of adult compared to 14-day-old rats. In contrast, bile acid concentrations were 10-fold higher in the peripheral serum of developing versus adult rats. The peripheral to portal serum bile acid concentration ratio was 0.23 in the adult and 6.48 in the 14-day-old rat. We conclude that the entire hepatic lobule participates in the uptake of bile acids in the 14-day-old rat even under the basal conditions of this study. The normal "reserve" function of centrilobular hepatocytes is not sufficient to compensate for the decreased transport capacity of the developing liver with the result that increased concentrations of bile acids enter and accumulate in the systemic circulation.