Portions of this work were presented at the Annual Meeting of the American Gastroenterological Society, New Orleans, Louisiana, May 14–20, 1988.
Chronic ethanol administration impairs receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes†
Article first published online: 6 DEC 2005
Copyright © 1990 American Association for the Study of Liver Diseases
Volume 12, Issue 5, pages 1085–1091, November 1990
How to Cite
Dalke, D. D., Sorrell, M. F., Casey, C. A. and Tuma, D. J. (1990), Chronic ethanol administration impairs receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes. Hepatology, 12: 1085–1091. doi: 10.1002/hep.1840120502
- Issue published online: 6 DEC 2005
- Article first published online: 6 DEC 2005
- Manuscript Accepted: 24 APR 1990
- Manuscript Received: 5 DEC 1989
- Department of Veterans Affairs
- National Institute on Alcohol Abuse and Alcoholism. Grant Number: AA04961
The effects of chronic ethanol administration on the receptor-mediated endocytosis of epidermal growth factor were studied in isolated rat hepatocytes. In initial experiments, it was demonstrated that significantly less ligand was bound by hepatocytes isolated from rats fed an ethanol liquid diet for 5 to 7 wk than by cells isolated from chow-fed or pair-fed controls. Reduced binding was shown to be primarily caused by a decreased number of surface receptors rather than by changes in receptor affinity. When hepatocytes were incubated at 37° C in the presence of a large saturating concentration of epidermal growth factor (80 nmol/L), intracellular levels of the ligand were significantly lower in cells from the ethanol-fed animals. However, no effect on degradation of the ligand was observed under those conditions. A defect in the initial stages of receptor-ligand internalization was also indicated because less surface-bound ligand was internalized and subsequently degraded in cells from the ethanoltreated rats. When the endocytosis of a lower, more physiological concentration of the growth factor (0.5 nmol/L) was studied, both the uptake of ligand and its degradation were markedly impaired in hepatocytes from the ethanol-fed animals. These results indicate that chronic ethanol administration impairs the receptor-mediated endocytosis of epidermal growth factor by the liver. The major impairment appears to be a reduction of cell surface receptors; however, other steps of the endocytotic pathway also appear to be affected. These altered steps include defective receptor-ligand internalization and changes in intracellular processing of the ligand leading to decreased degradation. (HEPATOLOGY 1990;12:1085–1091).