Ethanol-induced impairments in receptor-mediated endocytosis of asialoorosomucoid in isolated rat hepatocytes: time course of impairments and recovery after ethanol withdrawal.
Chronic ethanol administration markedly impairs the process of receptor-mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver. In this study, we further characterized these impairments by identifying the time of onset for ethanol-induced changes in RME as well as establishing the time course for recovery to normal endocytotic values after ethanol withdrawal. Ethanol administration for 3 days did not alter any aspect of endocytosis examined in this study. After feeding ethanol to rats for 7 days, however, significant decreases in amounts of ligand bound, internalized, and degraded were apparent. These impairments persisted throughout the 5-week feeding study although the effects were somewhat attenuated with more prolonged ethanol feeding. In addition, an accumulation of intracellular receptors was observed in ethanol-fed animals relative to controls after 7 days of ethanol feeding. In all cases, recovery of endocytotic values to control levels was partially completed after 2 to 3 days of refeeding control diet and was fully completed after 7 days of refeeding. These results indicate that ethanol feeding for as little as 7 days profoundly impairs the process of RME by the liver. These impairments can be reversed after refeeding control diet for 7 days.
Casey
C A
CA
Liver Study Unit, VA Medical Center, Omaha, NE 68105.
Kragskow
S L
SL
Sorrell
M F
MF
Tuma
D J
DJ
D000818:Animals; D001212:Asialoglycoproteins; D004705:Endocytosis / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D001212:Asialoglycoproteins; D007457:Iodine Radioisotopes; D009961:Orosomucoid; C017030:asialoorosomucoid; D000431:Ethanol