Understanding and controlling hepatobiliary function.

Abstract

Over the past decade, enormous progress has been made in identifying the mechanisms that underlie hepatobiliary excretion. A set of transport proteins mediates the canalicular transport of most important bile constituents. With the discovery of these transporter genes, the mechanism of bile formation could be partly elucidated and genetic defects caused by mutations in these genes identified. This progress is crucial not only for paediatric and adult hepatology, but also for pharmacology, because the characterization of these transport systems provides tools for the prediction of the pharmacokinetics of drugs. Indeed, there is a growing interest on the part of the pharmaceutical industry for research into transport systems in general and hepatobiliary secretion in particular. For all of these transporter genes, knockout mice have been bred that allow one to assess the in vivo function of each of these transporters with regard to their role in physiology and drug elimination.