Zymogen granule alterations in caerulein-induced pancreatitis developed during continuous hydrocortisone administration

Background The amount of enzymes stored in individual zymogen granules and the glycosylation of their membrane have been analysed in rats with acute p ancreatitis induced by caerulein after hydrocortisone treatment. The conseq uences of prolonging hydrocortisone administration after pancreatitis and t he use of the cholecystokinin (CCK) receptor antagonist, L364,718, have als o been evaluated. Materials and methods Analysis was performed using flow cytometry. Results Caerulein-induced pancreatitis in rats previously treated for 7 day s with hydrocortisone (10 mg kg(-1) per day) revealed alterations in enzyme storage in the pancreas. Significant increases in amylase and trypsinogen contents in zymogen granules were observed, an effect associated with a red uction in L-fucose glycoconjugates. Pancreatitis persists 7 days later if h ydrocortisone treatment is prolonged. At this stage, a reduced granule fuco sylation was still observed, and a significant decrease in the amount of tr ypsinogen stored in the granules was found. However, hydrocortisone adminis tration led to an increase in intragranular amylase quantities up to normal values, even when L364,718 was simultaneously administered, but it reverte d to plasma as a consequence of pancreatitis. The amount of N-acetyl D-gluc osamine in the zymogen granule membrane was not altered by caerulein acute pancreatitis induced under continuous hydrocortisone treatment, but it was decreased by the administration of L-364,718 over 7 days after pancreatitis induction. Conclusions The administration of hydrocortisone after the development of p ancreatitis prevented recurrence of the disease. L364,718 proved to be detr imental, not only failing to reduce the symptoms of pancreatitis but also a ltering the glycoproteins of zymogen granule membrane.