CHRONIC ETHANOL ADMINISTRATION SELECTIVELY IMPAIRS ENDOCYTOSIS IN THERAT EXOCRINE PANCREAS

Release of GP2, a glycosyl phosphatidylinositol-linked protein on the apical plasma membrane of the pancreatic acinar cell, is associated wi th activation of endocytosis. Released GP2 is also an integral compone nt of intraductal plugs in patients with alcohol-induced chronic pancr eatitis. Our purpose was to determine the effect of ethanol on exocyto sis and endocytosis and its association with release of membrane-bound GP2. Rats were fed Lieber-DeCarli diets with and without ethanol for 2 weeks. Endocytosis was then assessed in acini by measuring horseradi sh peroxidase (HRP) uptake, GP2 release by Western blotting, and exocy tosis by measuring amylase release. In ethanol-fed rats, HRP uptake wa s inhibited by 90% compared to that in control rats. In contrast, no s ignificant difference in cholecystokinin-stimulated amylase secretion was found. In vitro, ethanol inhibited HRP uptake in a dose-dependent manner, with 50% inhibition at 50 mM ethanol. Despite the inhibition o f endocytosis, GP2 release increased linearly over 60 min and was sign ificantly higher from acini incubated with ethanol compared to control s. These data indicate that ethanol selectively inhibits endocytosis i n pancreatic acinar cells. The release of GP2 into the pancreatic duct was no longer coupled to endocytosis in animals fed ethanol.