Ethanol feeding causes inactivation of both state 1 and state 2 rat hepatic asialoglycoprotein receptors.
Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of approximately 50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function, Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs.
Tworek
B L
BL
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Oka
J A
JA
Casey
C A
CA
Weigel
P H
PH
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D037263:Asialoglycoprotein Receptor; D004705:Endocytosis / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D008297:Male; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*
D037263:Asialoglycoprotein Receptor; D011956:Receptors, Cell Surface; D010171:Palmitoyl Coenzyme A; D000431:Ethanol; D000255:Adenosine Triphosphate