Autoradiographic evidence for hepatic lobular concentration gradient of bile acid derivative

Using an iodinated bile-acid analog with hepatic uptake and transport characteristics similar to conventional bile acids, the hepatic lobular gradient concept of Goresky was studied utilizing autoradiography. 125I-labeled cholylglycylhistamine (125I-CGH) was infused into the portal veins of male Sprague-Dawley rats and the livers were fixed for light microscopic autoradiography at 1 and 5 min after infusion. In two animals, sequential samples of bile were collected to assess the transport characteristics of 125I-CGH. By 1 min, virtually all (98%) of the injected 125I-CGH was taken up and retained by hepatocytes after perfusion fixation. Less than 15% of the label was lost during subsequent tissue processing. 125I-CGH appeared in bile within minutes, reaching maximum levels at 7 min. Quantitative autoradiography demonstrated that the first six to nine periportal hepatocytes were, by far, the most active (P less than 0.0005) in sequestering the bile-acid analog than were the remaining cells in the lobule. This study, therefore, provides the first autoradiographic evidence of a hepatic lobular concentration gradient for the uptake of a bile-acid analog.