The recovery of acute pancreatitis depends on the enzyme amount stored in zymogen granules at early stages

Little is known about the changes in pancreatic enzyme storage in acute pan creatitis. We have performed flow cytometric studies of zymogen granules fr om rats with acute pancreatitis induced by hyperstimulation with caerulein. A comparison was made with rats treated with hydrocortisone (10 mg/kg/day) over 7 days before inducing pancreatitis in order to find out whether the amount of enzymes stored in the pancreas plays a key role in the developmen t of pancreatitis. The potentially therapeutic effect of L-364,718 (0.1 mg/ kg/day, for 7 days), a CCK receptor antagonist, was assayed in the rats wit h caerulein-induced pancreatitis which had previously received the hydrocor tisone treatment. A significant increase in the intragranular enzyme conten t was observed 5 h after hyperstimulation with caerulein. The highest value s were reached in the rats previously treated with hydrocortisone. The grea test pancreatic enzyme load was parallel to the highest values in plasma am ylase, edema and haematocrit observed. Acute pancreatitis was reversed seve n days later. At this stage smaller granules appeared in the pancreas whose enzyme content was similar to that of controls when no treatment was appli ed after pancreatitis. In contrast, L-364,718 administration prevented the favourable evolution of pancreatitis since the antagonism exerted on CCK re ceptors induced a blockade of secretion of the large amounts of enzymes sto red in the pancreas. Moreover, the enzyme content in zymogen granules was b elow normal values since the stimulatory CCK action on enzyme synthesis can be inhibited by L-364,718. Our results suggest that the efficiency of CCK antagonists, as potential therapy, would also depend on the load of enzymes in the pancreas when acute pancreatitis is produced.