Effects of ethionine on digestive enzyme synthesis and discharge by mouse pancreas

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Abstract
Earliest changes of pancreatitis induced by feeding mice a choline-deficient ethionine-supplemented (CDE) diet were increasedly number of zymogen granules in pancreatic acinar cells and increased digestive enzyme content of pancreas. Processes of protein and digestive enzyme synthesis and discharge at varying times after institution of CDE diet, a choline-deficient diet (CD) and a diet containing ethionine but not choline-deficient (E) were studied. Both CDE and E diets increased digestive enzyme content within 12 h. Both diets reduced the rate of protein and amylase synthesis and caused a marked reduction in rate of protein and amylase discharge from pancreas. These changes were greatest and noted earliest in CDE diet. A marked reduction in secretagogue-induced in vivo and in vitro amylase discharge followed ingestion of either CDE or E diet. Increased pancreatic content of digestive enzymes noted after ingestion of CDE and E diets resulted from an ethionine-induced decrease in rate of digestive enzyme discharge. This phenomenon was enhanced by simultaneous choline deficiency. Subsequent intrapancreatic activation of zymogens coupled these changes in enzyme content to development of hemorrhagic pancreatitis.