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 pancreatitis and in the early recovery phase of acute pancreatitis were investigated in rats with closed duodenal loop (CDL)-induced pancreatitis. The subcutaneous injection of CCK-8 (2 mu g/kg) stimulated a physiological level of pancreatic enzyme secretion in normal control rats, but did not lead to any biochemical or histological evidence of acute pancreatitis. A higher dose of CCK-8 (8 mu g/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal 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 biochemical nor the histological findings of acute pancreatitis showed any progression compared with the changes in controls given no CCK-8. Serum CCK 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 the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the admistration of 2 mu g/kg of CCK-8 to rats upon release 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 histological 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 acute pancreatitis, and neither CCK treatment had any adverse effect on the early recovery phase of CDL-induced acute pancreatitis. A pharmacological dose of CCK, however, exacerbated the acute pancreatitis, even in the early recovery stage.