Differential effects of monensin on asialoglycoprotein receptor function after short-term ethanol administration

Benita L. Tworek, Robert L. Wiegert, Joseph P. Jeanette, Dean J. Tuma, Carol A. Casey

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Chronic ethanol consumption is associated with multiple impairments in receptor-mediated endocytosis (RME) by the hepatic asialoglycoprotein receptor (ASGP-R). Previous work on this receptor has shown that its activity can be perturbed by the carboxylic ionophore monensin. This agent has been shown to preferentially affect receptor-ligand dissociation and receptor redistribution of one subset (State 2) of ASGP-R, while receptor function in a second subset (State 1 receptors) is unaffected. In the present study, we examined the effect of monensin on ASGP-R activity and intracellular receptor-ligand dissociation after 7-10 days of ethanol feeding, a time when we have shown altered ASGP-R function in ethanol-fed animals. Hepatocytes from male Wistar rats (fed an ethanol-containing or control diet) were utilized. Ethanol administration decreased total ligand binding by 35-40% (P < 0.01) without a change in receptor protein content. After monensin treatment, surface receptors on cells from control animals were inactivated and redistributed to the cell interior. In cells from ethanol-fed animals, a similar pattern of monensin-induced inactivation was shown, but no redistribution occurred. Intracellular receptor-ligand dissociation was impaired in both cell types, although the monensin-induced effect on dissociation was significantly less dramatic (two-fold) in the hepatocytes from ethanol-fed animals as compared with controls. Thus, although receptors on both cell types were susceptible to monensin, cells from the ethanol-fed animals were less vulnerable to the added effects of this agent. Since monensin affects functioning of State 2, but not State 1 receptors, a very early effect of ethanol may be a preferential impairment in the State 2 receptor population.

Original languageEnglish (US)
Pages (from-to)1603-1609
Number of pages7
JournalBiochemical Pharmacology
Volume55
Issue number10
DOIs
StatePublished - May 15 1998

Keywords

  • Alcohol
  • Asialoglycoprotein receptor
  • Endocytosis
  • Liver
  • Monensin

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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