Modulation of asialoglycoprotein receptor levels in rat liver by phenobarbital treatment

The effect of the liver tumor promoter, phenobarbital, on thelevel of the asialoglycoprotein receptor (ASGP-R) was examinedin adult rat liver. ASGP-R, a liver-specific cell surface membraneprotein, was studied using antibody against this receptor togetherwith immunofluorescence techniques and radioreceptor assay withasialofetuin as the ligand. Both acute and chronic phenobarbitaladministration decreased the number of receptors per cell; partialhepatectomy had a similar effect on the number of receptorsper cell. However, after phenobarbital administration, the receptor-deficientareas were centrilobular, whereas after partial hepatectomy,ASGP-R positive and negative areas were intermingled throughoutthe liver lobule but were most pronounced in the periportalarea. Phenobarbital treatment, in contrast to its effect onthe ASGP-R level, did not change the cell surface binding ofconcanavalin A on rat hepatocytes. Four days after birth thenumber of hepatocytes with surface receptors was 50% of thatin the adult rats. At 10 days after birth the number of ASGP-Rpositive cells was the same as in adult rats, although the receptordensity was significantly lower than in adults. Treatment witha single dose of chemical carcinogen one day after birth combinedwith promotion by phenobarbital resulted in a significant reductionof ASGP-Rs in pre-neoplastic and neoplastic areas of livers.Whereas the pre-neoplastic and neoplastic areas displayed uniformreduction in the ASGP-R, normal parts of the liver showed receptor-deficiencyprimarily in the centrilobular areas.