Postulated mechanisms of
alcoholic pancreatitis include (i) zymogen granule fragility facilitating intracellular activation of digestive
enzymes and (ii) ductular obstruction by
protein plugs. GP2, a pancreatic
glycoprotein, stabilizes zymogen granule membranes and is an important constituent of pancreatic
protein plugs. Therefore, this study examined the pancreatic content and
messenger RNA levels of GP2 after chronic
ethanol administration. Rats were fed liquid diets with or without
ethanol, for four weeks. GP2 levels in pancreatic homogenates, crude zymogen granules and zymogen granule membrane fractions were assessed by immunoblotting.
Messenger RNA levels for GP2 were measured by Northern and dot blotting of pancreatic
RNA. Pancreatic GP2 levels were lower in
ethanol-fed rats than in controls (GP2 levels expressed as % of control: 38.75 +/- 5.8, p < 0.001 in homogenate; 31.28 +/- 3.5, p < 0.0005 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) result from an increased release into pancreatic juice thereby favouring
protein plug formation and (ii) impair zymogen granule stability. Both these mechanisms could potentiate pancreatic damage.