Increased Circulating Cholecystokinin in Obstruction-Induced Acute Pancreatitis

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

“…In 6-hr pancreatic duct ligation-induced pancreatitis, administration of T-0632 partially prevented both the increase in plasma amylase activity and the histological changes in the pancreas. Partially preventive effects of CCKA-receptor antagonists in this model have also been reported by others (10)(11)(12). On the other hand, CCKA-receptor antagonists have been reported to have no preventive effect on long-term pancreatic duct ligation induced pancreatitis (10).…”

CCK-A receptor induction and P38MAPK and NF-κB activation in acute pancreatitis

“…Using a unique and original surgical model, the Donor Rat Model, we have also shown that duodenal replacement of bilepancreatic juice -obtained fresh from a donor ratachieves substantial amelioration of ligation-induced acute pancreatitis in rats [1]. In another study, we showed that combined CCK-A and muscarinic receptor blockade ameliorates acinar hyperstimulation in the same experimental model [2,32]. Based on these observations, we suggested that bile-pancreatic juice exclusion-induced acinar cell hyperstimulation in the presence of duct obstruction exacerbates acute pancreatitis via CCK-A and muscarinic receptor-mediated pathways.…”

Role of Cholecystokinin in the Development and Progression of Acute Pancreatitis and the Potential of Therapeutic Application of Cholecystokinin Receptor Antagonists

“…Several recent studies [8, 9, 10]have reported that circulating CCK is increased after pancreaticobiliary obstruction in rats. The ligation of the pancreaticobiliary duct in the rat caused a slight but significant increase in plasma CCK probably due to the decrease in secretion of enzymes and bile salts caused by feedback mechanisms.…”

“…There are, however, also models in which endogenous CCK is released to cause an increase in plasma CCK values. These models include pancreaticobiliary obstruction in rats [8, 9, 10]and duodenal loop-induced pancreatitis in rats [11]. The experimental manipulations in both models lead to a decrease in duodenal concentrations of digestive enzymes and bile salts which are known to cause a release of duodenal CCK and thereby to increase its circulating concentration via a previously established feedback mechanism [12, 13, 14, 15, 16].…”