Influence of ductal pressure and infusates on activity and subcellular distribution of lysosomal enzymes in the rat pancreas

Abstract Background & Aims: Subcellular redistribution of lysosomal enzymes into the zymogen-enriched fraction (cosedimentation) in pancreatic homogenates occurs after different pancreatic injuries and has been proposed to be the trigger event for acute pancreatitis. This phenomenon is now studied in models of biliary pancreatitis. Methods: The bile-pancreatic duct in rats was either obstructed or retrogradely infused at different degrees of pressure and with solutions of various injurious potential. Controls were untreated or sham operated. Six hours later, the pancreas was analyzed for the total activity of cathepsin B and β-galactosidase and their distribution among subcellular fractions. Results: In control animals, 17% and 29%, respectively, of these lysosomal enzymes were found in the zymogen fraction. Redistribution occurred after all duct manipulations, including obstruction. In contrast to sham operation and duct obstruction, all modes of duct infusion resulted in marked increases in the total activity of lysosomal enzymes. Conclusions: Increased lysosomal activity in models of biliary pancreatitis might contribute to acinar injury or represent a cellular repair mechanism. Cosedimentation at a certain extent is a physiological event. Redistribution reflects a uniform response to a range of perturbations, some of which do not cause pancreatitis. Thus, it seems unlikely that redistribution is the trigger event for acute pancreatitis.