Effects of ethanol on the secretion of glycoproteins by rat liver slices

The effects of ethanol on the metabolism of microsomal glycoproteins and the secretion of export glycoproteins by rat liver slices were investigated and compared to the effects of colchicine, a known inhibitor of glycoprotein secretion. Both ethanol (10 mM) and colchicine (50 μM), when present in the incubation medium, markedly decreased the appearance of [¹⁴C]glucosamine-labeled proteins in the medium. However, when microsomes were isolated and fractionated into a fraction rich in nonmembranous secretory glycoproteins and another fraction rich in membrane bound glycoproteins, the effects of these agents on the labeling of glycoproteins of these two microsomal fractions differed. Colchicine did not affect the incorporation of glucosamine into the membrane fraction but increased the labeling of the secretory fraction, whereas, ethanol decreased incorporation into the membrane fraction without altering the labeling of the secretory fraction. When protein synthesis was inhibited by cycloheximide, both ethanol and colchicine markedly reduced the appearance of glucosamine-labeled proteins in the medium and concomitantly increased the specific activity of the glycoproteins of the secretory fraction of microsomes without altering the labeling of membrane glycoproteins. When fucose, a terminal sugar whose short-term incorporation into glycoproteins is not dependent on protein synthesis, was used as a label, both agents decreased the appearance of fucose-labeled proteins in the medium while also causing a retention of fucose-labeled glycoproteins in the microsomal secretory fraction. Ethanol did not affect fucose labeling of microsomal membrane glycoproteins; however, colchicine did cause a slight increase. These results indicate that both ethanol and colchicine inhibit hepatic glycoprotein secretion; however, since ethanol inhibits protein synthesis, acute ethanol administration, unlike colchicine, does not result in the intrahepatic accumulation of non-secreted glycoproteins.