DECREASED BINDING OF ASIALOGLYCOPROTEINS TO HEPATOCYTES FROM ETHANOL-FED RATS - CONSEQUENCE OF BOTH IMPAIRED SYNTHESIS AND INACTIVATION OF THE ASIALOGLYCOPROTEIN RECEPTOR

Chronic ethanol administration alters the process of receptor-mediated endocytosis in isolated rat hepatocytes, Using the asialoglycoprotein receptor (ASGP-R) as a model, we have previously shown decreased bind ing of asialoglycoproteins to this receptor after as early as 1 week o f ethanol administration, In the present study, we further analyzed th e mechanism(s) responsible for this impairment by determining the liga nd and antibody binding characteristics of the ASGP-R in rats fed etha nol over a B-week time course, The results presented here demonstrate that ethanol treatment for 4 days significantly impaired total ligand binding without affecting antibody binding, Ethanol administration for a longer period of 1-2 weeks resulted in intermediate impairments in both ligand and antibody binding, After 5 weeks of ethanol exposure, l igand and antibody binding were equally lowered, In contrast to total cellular receptor binding, surface binding of both ligand and antibody were decreased over the entire time course of ethanol administration. Our data indicate that the ASGP-R is initially inactivated during the time course of ethanol exposure and that a redistribution of surface receptors to intracellular compartments occurs. Northern blot analysis showed that there was a significant decrease in receptor mRNA content in the 5-week chronically fed animals but not in the animals fed for 1 week. In addition, after 5 weeks of ethanol feeding, biosynthetic la beling of the ASGP-R was decreased in the ethanol cells, indicating im paired synthesis of the ASGP-R. In summary, an early inactivation of t he ASGP-R occurs during ethanol exposure followed by an actual decreas e in protein and mRNA content for the receptor.