ROLE OF ENDOGENOUS AND EXOGENOUS CHOLECYSTOKININ IN EXPERIMENTAL ACUTE-PANCREATITIS INDUCED IN RATS BY THE DUODENAL LOOP TECHNIQUE

The role of endogenous cholecstokinin (CCK) release and exogenous CCK- 8 administration in the development and progression of acute pancreati tis and in the early recovery phase of acute pancreatitis were investi gated in rats with closed duodenal loop (CDL)-induced pancreatitis. Th e subcutaneous injection of CCK-8 (2 mu g/kg) stimulated a physiologic al level of pancreatic enzyme secretion in normal control rats, but di d not lead to any biochemical or histological evidence of acute pancre atitis. A higher dose of CCK-8 (8 mu g/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the nor mal control rats. When 2 mu g/kg of CCK-8 was injected subcutaneously in rats 6 and 12h after the creation of the CDL, neither the biochemic al nor the histological findings of acute pancreatitis showed any prog ression compared with the changes in controls given no CCK-8. Serum CC K levels, measured by radio-immunoassay, increased significantly from mean levels of 5.39pg/ml (+/-0.95 SD) before creation of the CDL to 42 .06pg/ml (+/-2.27 SD) 6h after, and 41.95pg/ml (+/-1.88 SD) 12h after its creation (P < 0.01). The difference between serum CCK levels at 6 and 12h was not statistically significant. Following the release of th e loop, serum CCK levels decreased gradually, especially in rats in wh ich the loop was released 6h after being created. Although no marked b iochemical and histological changes of acute pancreatitis were observe d following the admistration of 2 mu g/kg of CCK-8 to rats upon releas e of the loop 6h and 12h after its creation, a higher dose of CCK-8 (8 mu g/kg) in these rats adversely affected both the biochemical and hi stological findings of acute pancreatitis. Based on these findings, it was concluded that neither endogenous CCK release, as a result of the CDL, nor physiological stimulation of the pancreas by exogenous CCK-8 administration, caused progression from edematous to hemorrhagic acut e pancreatitis, and neither CCK treatment had any adverse effect on th e early recovery phase of CDL-induced acute pancreatitis. A pharmacolo gical dose of CCK, however, exacerbated the acute pancreatitis, even i n the early recovery stage.