Effect of ethanol on gastric mucus glycoprotein synthesis, translocation, transport, glycosylation, and secretion.
The effect of ethanol on mucus glycoprotein synthesis, intracellular modification, transport, glycosylation, and secretion was studied in rat gastric mucous cells. Preincubation of the in vitro translation mixture containing gastric mucous cells mRNA for 60 min with 0 to 120 mM ethanol caused a decrease in the synthesis of mucus glycoprotein apopeptide by up to 40%. The reduction in translation was time- and ethanol concentration-dependent. After 60 min, translation in the presence of 30, 60, and 120 mM ethanol decreased to 83.3 +/- 2.3%, 75.5 +/- 0.4%, and 63.6 +/- 2.6%, respectively. The experiments conducted with endoplasmic reticulum microsomes, preincubated with ethanol, and used in the studies of cotranslational translocation of the apomucin showed a 20% decrease in the transfer of mucus glycoprotein apopeptide to the lumen of endoplasmic reticulum microsomes. In the presence of ethanol, processing of mucus glycoprotein apopeptide in Golgi was also inhibited. During the initial 30 min of incubation with 0 to 120 mM ethanol, glycosylation seemed to proceed at the same rate in the samples with and without ethanol. However, during consecutive 30 min of incubation, glycosylation in the presence of 60 mM ethanol decreased by 30 to 35%, and with 120 mM ethanol was completely inhibited. Measurements of the effect of ethanol on the discharge of mucus glycoprotein from the intracellular stores revealed that, on average, the secretory output of the rat gastric mucosa exposed to ethanol liquid diet for 8 weeks decreased by 77% or more, and adherence of the glycoprotein to the gastric epithelium was weakened. Results indicate that ethanol inhibits synthesis, transport, and processing of gastric mucus glycoprotein, and that the processes taking place in different intracellular compartments contribute in the additive fashion and, are reflected in a dramatic decrease in the delivery of mucus glycoprotein to the gastric epithelial surfaces.