Modulation of asialoglycoprotein receptor levels in rat liver by phenobarbital treatment

Abstract

The effect of the liver tumor promoter, phenobarbital, on the level of the asialoglycoprotein receptor (ASGP-R) was examined in adult rat liver. ASGP-R, a liver-specific cell surface membrane protein, was studied using antibody against this receptor together with immunofluorescence techniques and radioreceptor assay with asialofetuin as the ligand. Both acute and chronic phenobarbital administration decreased the number of receptors per cell; partial hepatectomy had a similar effect on the number of receptors per cell. However, after phenobarbital administration, the receptor-deficient areas were centrilobular, whereas after partial hepatectomy, ASGP-R positive and negative areas were intermingled throughout the liver lobule but were most pronounced in the periportal area. Phenobarbital treatment, in contrast to its effect on the ASGP-R level, did not change the cell surface binding of concanavalin A on rat hepatocytes. Four days after birth the number of hepatocytes with surface receptors was 50% of that in the adult rats. At 10 days after birth the number of ASGP-R positive cells was the same as in adult rats, although the receptor density was significantly lower than in adults. Treatment with a single dose of chemical carcinogen one day after birth combined with promotion by phenobarbital resulted in a significant reduction of ASGP-Rs in pre-neoplastic and neoplastic areas of livers. Whereas the pre-neoplastic and neoplastic areas displayed uniform reduction in the ASGP-R, normal parts of the liver showed receptor-deficiency primarily in the centrilobular areas.