Differential colchicine effects on the transport of membrane and secretory proteins in rat hepatocytes in vivo: bipolar secretion of albumin.
We carried out a comparative investigation on the effects of colchicine (25 mumoles/100 gm body wt) on the intracellular transport, processing and discharge by secretion or proteolytic processing of a membrane protein (i.e., the polymeric IgA receptor) and a secretory protein (i.e., albumin) in rat hepatocytes. The results obtained indicated the following: (a) the transport and processing of polymeric IgA receptor is strongly inhibited and delayed, but the appearance of secretory component in the bile is not arrested; (b) polymeric IgA receptor reaches the sinusoidal plasmalemma in colchicine-treated specimens, as it does in controls; (c) albumin discharge into the plasma is strongly inhibited and markedly delayed in colchicine-treated as compared with control animals; (d) the reverse applies for albumin secretion in the bile, which is increased by a large factor; (e) newly synthesized albumin secreted directly from hepatocytes in control and in colchicine-treated animals is the major source of bile albumin; and (f) colchicine affects in different ways the polymeric IgA receptor and albumin arrival at the sinusoidal front and especially at the biliary front of the hepatocyte.
Saucan
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Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093.
Palade
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GE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*
C045281:IgA receptor; D008565:Membrane Proteins; D011108:Polymers; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D012709:Serum Albumin; D003078:Colchicine