Effects of trypsin, chymotrypsin, and uncoupling on survival of isolated acinar cells from rat pancreas
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To improve the knowledge of the very complex pathogenesis of acute pancreatitis, separated exocrine pancreatic cells were used as an experimental tool. Intact acinar cells were isolated from rat pancreas and the time course of their damage was studied in the presence of increasing activities of trypsin, chymotrypsin and, after, stepwise uncoupling of oxidative phosphorylation, by 2,4-dinitrophenol (DNP). With an increasing degree of uncoupling the half-life period of cells incubated was remarkably reduced. Extracellular trypsin, present in activities comparable with the endogenous trypsinogen content, was not effective in cell killing. Only when the trypsin activity was drastically enhanced was the rate of cell destruction accelerated. Compared with chymotrypsin, isolated acinar cells revealed some resistance to extracellular trypsin. But when the energy production was altered by partial uncoupling the susceptibility of these cells toward the action of trypsin was increased and their life time was remarkably reduced.
The potentiation of the effects of trypsin and uncoupling on cell viability demonstrates the contribution of an intact energy metabolism to the protective potential of acinar cells against further noxae.
Key WordsAcute pancreatitis cell damage energy metabolism pancreatic proteases pathogenesis
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