Role of intracellular organelles in the hepatic transport of bile acids.
The intracellular events associated with the vectorial transport of bile acids by the hepatocytes from the sinusoidal pole to the canalicular pole are reviewed. Binding to cytosolic proteins occurs. The role of this binding is to prevent efflux from the cytosol back into the blood. There is evidence from electron microscopy, from autoradiography and from immunoperoxidase observations that bile acids interact with the endoplasmic reticulum and the Golgi apparatus. There is also evidence that a carrier system or taurocholate exists on the Golgi membrane. We propose that a vesicular pathway involving the Golgi apparatus and dependent on the integrity of microtubules may play a role in bile acid transport in the cell. Inhibition of bile acid transport by microtubule poisons is consistent with this hypothesis. Finally, monohydroxylated, cholestatic bile acids such as lithocholate and taurolithocholate interact with the endoplasmic reticulum. This interaction results in a depletion of the endoplasmic reticulum calcium stores and an increase in intracellular ionized calcium. The relationship of this novel effect of bile acids to their cholestatic properties remains to be elucidated.
Erlinger
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Service d'Hépatologie, INSERM U-24, Hôpital Beaujon, Clichy, France.
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism / Q000493:pharmacokinetics*; D002779:Cholestasis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D015388:Organelles / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
D001647:Bile Acids and Salts