CHRONIC ETHANOL ADMINISTRATION DECREASES RAT PANCREATIC GP2 CONTENT

Postulated mechanisms of alcoholic pancreatitis include (i) zymogen gr anule fragility facilitating intracellular activation of digestive enz ymes and (ii) ductular obstruction by protein plugs. GP2, a pancreatic glycoprotein, stabilizes zymogen granule membranes and is an importan t constituent of pancreatic protein plugs. Therefore, this study exami ned the pancreatic content and messenger RNA levels of GP2 after chron ic ethanol administration. Rats were fed liquid diets with or without ethanol, for four weeks. GP2 levels in pancreatic homogenates, crude z ymogen granules and zymogen granule membrane fractions were assessed b y immunoblotting. Messenger RNA levels for GP2 were measured by Northe rn and dot blotting of pancreatic RNA. Pancreatic GP2 levels were lowe r in ethanol-fed rats than in controls (GP2 levels expressed as % of c ontrol: 38.75 +/- 5.8, p < 0.001 in homogenate; 31.28 +/- 3.5, p < 0.0 005 in crude zymogen granules and 22.89 +/- 5.4, p < 0.0005 in zymogen granule membranes). Messenger RNA levels for GP2 were unchanged after ethanol feeding. Chronic ethanol consumption decreases GP2 content of pancreatic homogenate and zymogen granules. This decrease could (i) r esult from an increased release into pancreatic juice thereby favourin g protein plug formation and (ii) impair zymogen granule stability. Bo th these mechanisms could potentiate pancreatic damage. (C) 1997 Elsev ier Science B.V.