The effects of chronic ethanol administration on the rates of internalization of various ligands during hepatic endocytosis.
The purpose of the present study was to further characterize the ethanol-induced impairments in hepatic endocytosis. Specifically, we examined the effects of ethanol treatment on receptor-ligand internalization via the coated and noncoated pit pathways. Insulin, epidermal growth factor (EGF) and asialoorosomucoid (ASOR) were used as model ligands to study internalization by isolated hepatocytes. ASOR and EGF are thought to be internalized strictly in coated pit regions of the cell membrane, while insulin may be internalized in both coated and uncoated membrane regions. Ethanol administration for 5-7 weeks decreased internalization of ASOR and EGF while internalization of insulin was unchanged during a single round of endocytosis of surface-bound ligand. Similarly, a more quantitative measure of endocytosis, the endocytic rate constant, was decreased for EGF and ASOR but not for insulin in livers of experimental rats. When endocytosis of Lucifer yellow, a fluorescent dye known to be internalized in the cell by fluid-phase endocytosis was examined, the initial rates of dye uptake were not significantly altered by alcohol administration. These results indicate that ethanol may selectively impair internalization occurring by coated pits while it has a minimal effect on initial uptake of molecules which are internalized by noncoated membrane regions.
Casey
C A
CA
Liver Study Unit, Department of Veterans Affairs Medical Center, Omaha, NE 68105.
Camacho
K B
KB
Tuma
D J
DJ
D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D005456:Fluorescent Dyes; D007328:Insulin / Q000378:metabolism*; D007546:Isoquinolines / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats
D001212:Asialoglycoproteins; D005456:Fluorescent Dyes; D007328:Insulin; D007546:Isoquinolines; D008024:Ligands; D009961:Orosomucoid; C017030:asialoorosomucoid; D000431:Ethanol; D004815:Epidermal Growth Factor; C017475:lucifer yellow