Zonal differences in ethanol-induced impairments in hepatic receptor binding.
We have previously shown ethanol-induced defects in receptor-mediated endocytosis of asialoorosomucoid (ASOR), epidermal growth factor (EGF), and insulin in isolated rat hepatocytes. The present study was undertaken to compare the binding of these three ligands in both Zone 1 (periportal [PP] region) and Zone 3 (perivenule [PV] region) of rat liver. Cells from the PV region of ethanol-fed animals bound significantly less EGF (40% decrease) than did cells from the same area in control rats. EGF binding was decreased to a lesser extent (15-25%) in PP cells from ethanol-fed animals compared to controls. When binding of ASOR was examined, ethanol feeding significantly impaired binding in both PP cells (30-35% decrease) and PV cells (50-55% decrease), again showing a greater ethanol-induced impairment in the PV region. Insulin binding in ethanol animals was decreased by 20-25% in both regions compared to controls. In addition, we found that ASOR receptor recycling was impaired to a greater extent in the PV than in the PP region of liver after ethanol feeding, indicating selective impairment of receptor function in the centrilobular region of the liver.
McCashland
T M
TM
Liver Study Unit, VA Medical Center, Omaha, NE 68105.
Tuma
D J
DJ
Sorrell
M F
MF
Casey
C A
CA
D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D001212:Asialoglycoproteins; D007328:Insulin; D009961:Orosomucoid; D011956:Receptors, Cell Surface; C017030:asialoorosomucoid; D000431:Ethanol; D004815:Epidermal Growth Factor