Inhibition of the endocytic pathway for asialoglycoprotein catabolism.
Rat hepatocytes in primary culture bind, internalize and eventually degrade asialoglycoproteins. This process is mediated by a specific receptor in the hepatocyte plasma membrane. The endocytic pathway by which ligand molecules are translocated to lysosomes has been examined by the development of biological assays capable of distinguishing ligand populations at various points in the process. Inhibitors have been identified that perturb particular transitions that define the endocytic pathway. In the present paper, inhibition by the bacterial tripeptide leupeptin is compared to the effect of colchine plus cytochalasin B. The latter combination impedes intracellular segregation of ligand and receptor while leupeptin inhibits intralysosomal proteolysis. However, evidence is presented to indicate that the inhibitory effects colchine plus cytochaasin B consists of at least two components. One component is independent of the presence of ligand whereas the other is observed only when ligand is present together with the drugs.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D009961:Orosomucoid / Q000031:analogs & derivatives; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D008024:Ligands; D009961:Orosomucoid; D011971:Receptors, Immunologic; D003571:Cytochalasin B; D003078:Colchicine