Mechanisms of secretion of proteins into bile: Studies in the perfused rat liver

Authors

  • Thomas M. Kloppel Ph.D.,

    Corresponding author
    1. Department of Medicine of the Veterans Administration Medical Center, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
    2. Department of Medicine and Biochemistry, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
    • Veterans Administration Medical Center (151), 1055 Clermont Street, Denver, Colorado 80220
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  • William R. Brown,

    1. Department of Medicine of the Veterans Administration Medical Center, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
    2. Department of Medicine and Biochemistry, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
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  • Juerg Reichen

    1. Department of Medicine of the Veterans Administration Medical Center, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
    2. Department of Medicine and Biochemistry, Biophysics and Genetics of the University of Colorado School of Medicine, Denver, Colorado 80220
    Current affiliation:
    1. Department of Clinical Pharmacology, University of Berne, CH-3010, Berne, Switzerland
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Abstract

Employing the in situ perfused rat liver, we examined the origins and mechanisms of transport of proteins into bile. First, utilizing polyacrylamide gels, we noted that many biliary proteins co-migrated with dominant serum proteins. Upon liver perfusion with serum-free medium, most proteins disappeared from the biliary profile; one major biliary protein that was not present in serum, identified as secretory component, remained. Kinetic analysis of the disappearance half-lives of the biliary proteins suggested that some serum proteins enter bile by a slow (20 to 30 min; transcellular) route, while others utilize both slow and rapid (5 min; paracellular) routes. In biosynthetic labeling experiments, secretion of newly synthesized proteins into bile was delayed about 20 min when compared with secretion of proteins into the perfusion medium and comprised less than 1% of the total secreted proteins. When a new liver was inserted into the perfusion medium containing newly synthesized secreted proteins, only two proteins, hemopexin and an unidentified protein, were transported into the bile from the perfusion medium; other biliary proteins were presumed to come directly from the hepatocyte. This latter group included some proteins that were secreted into the perfusion medium as well as into bile, and others, e.g., secretory component, that were secreted only into bile. Based on our results we have defined six pathways for entry of proteins into bile.

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