Effect of ethanol on pancreatic lysosomes in rats: a possible mechanism for alcoholic pancreatitis.

Four-hour infusion of ethanol (0.5 g/kg.hr) and additional 2-hour infusion of caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) caused hyperamylasemia, pancreatic edema and pancreatic histological changes such as interstitial edema and acinar cell vacuolization in the rat. Such a combined treatment also induced a redistribution of lysosomal enzyme cathepsin B, from the lysosomal fraction to the zymogen fraction in subcellular fractionation. Only ethanol infusion caused marginal changes in all these parameters. Moreover, 4-hour pre-infusion of ethanol caused a significant increase in pancreatic cathepsin B output stimulated by caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) compared with the control rats. This pretreatment of ethanol also caused a significant increase in cathepsin B/amylase output ratio. These results indicate that ethanol administration, if combined with exocrine stimulation, causes a colocalization of lysosomal hydrolases with digestive enzymes in the same subcellular compartment as well as in the pancreatic ductal space, and also suggest one possible mechanism for alcoholic pancreatitis both within and outside the acinar cells, since cathepsin B can activate trypsinogen.