Bile secretory apparatus: evidence for a vesicular transport mechanism for proteins in the rat, using horseradish peroxidase and [125I]insulin.
The morphologic mechanisms involved in the uptake, transport, and secretion of proteins into bile were studied in rat liver in vivo. When both horseradish peroxidase (HRP) and insulin were injected into the portal veins of anesthetized rats, these proteins were subsequently detected in bile. Utilizing the technique of combined cytochemistry and quantitative autoradiography, both HRP and [125I]insulin were coincidentally localized within endocytic vesicles within the interior of hepatocytes at various time points after simultaneous intraportal injection. The data suggest that both proteins followed two pathways involving endocytic vesicles of approximately 1000 A in diameter. In the first pathway these protein-containing vesicles were transported through the hepatocyte and subsequently fused with the bile canalicular membrane, resulting in secretion of contained proteins into the biliary space. The second pathway also involved endocytosis into 1000 A vesicles, but these vesicles were transported to the Golgi region and its associated system of lysosomes and endoplasmic reticulum (GERL). Whether the proteins in these vesicles were later secreted into bile was unclear. Measurement of HRP and [125I]insulin or its metabolites, in bile, provided direct evidence that exogenously administered proteins (or their fragments) gain entrance into the biliary space. Studies in which metabolites of [125I]insulin, [125I]monoiodotyrosine (MIT), and 125I, were injected intraportally, demonstrated that less than 10% of [125I]MIT and less than 1.5% of Na125I were retained in perfusion-fixed and processed liver tissue. This study suggests that proteins in blood plasma are taken up by hepatocytes and secreted into bile via a vesicular transport mechanism.
D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006651:Histocytochemistry; D006735:Horseradish Peroxidase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D007470:Monoiodotyrosine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D007457:Iodine Radioisotopes; D011506:Proteins; D006735:Horseradish Peroxidase; D007470:Monoiodotyrosine