Role of endogenous and exogenous cholecystokinin in experimental acute pancreatitis induced in rats by the duodenal loop technique.
The role of endogenous cholecystokinin (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 micrograms/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 micrograms/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal control rats. When 2 micrograms/kg of CCK-8 was injected subcutaneously in rats 6 and 12 h 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 5.39 pg/ml (+/- 0.95 SD) before creation of the CDL to 42.06 pg/ml (+/- 2.27 SD) 6 h after, and 41.95 pg/ml (+/- 1.88 SD) 12 h after its creation (P < 0.01). The difference between serum CCK levels at 6 and 12 h was not statistically significant. Following the release of the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6 h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the administration of 2 micrograms/kg of CCK-8 to rats upon release of the loop 6 h and 12 h after its creation, a higher dose of CCK-8 (8 micrograms/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.
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First Department of Surgery, Osaka City University Medical School, Japan.
Satake
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K
Hiura
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D000208:Acute Disease; D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D004386:Duodenum / Q000601:surgery; D006470:Hemorrhage / Q000209:etiology; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*; D013997:Time Factors
D002766:Cholecystokinin; D012844:Sincalide