The aim of this proposal is to characterize the driving forces that determine bile acid and other organic solute transport across sinusoidal and canalicular membrane domains in rat hepatocytes. Membrane vesicle systems will be utilized to determine these mechanisms and will be prepared from separate domains of the liver cell plasma membrane. Comparative studies of several membrane isolation procedures will be carried out to determine the optimal preparation. These studies should help elucidate for the first time, the mechanism of the liver to bile excretory step for organic solutes, the rate limiting step in the hepatic transport system. Ultimately, these studies should lead to an understanding of bile formation and excretion, a vital process which is impaired, often irreversibly, in many forms of liver injury in man.
