A new thrapy for severe acute pancreatitis by regulating the cannabinoid

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Cannabinoids are the pharmacologically essential components of marihuana. Anandamide (ANA) is one of the cannabinoids and it has recently become clear that anandamide is one of the mediators in septic shock. The pathogenesis of acute pancreatitis is not clearly understood and whether there is a relationship between acute pancreatitis and cannabinoids is unknown. Therefore, we aimed to clarify the relationship between acute pancreatitis and cannabinoids and to find a new therapy to regulate the cannabinoids in acute pancreatitis. Rats were injected with cerulein intravenously to induce mild edematous pancreatitis and were injected with 5% sodium taurochorate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. After the induction of pancreatitis, blood was collected to measure the plasma anandamide value by the LC/MS/MS method. Kidneys were stained immunohistochemically to evaluate the appearance of the cannabinoid receptor 1 (CBI receptor). Finally, rats were injected with the antagonist of the CB1 receptor (SR141716A) after the induction of severe acute pancreatitis to clarify the role of cannabinoids in the pathogenesis of acute pancreatitis. After the induction of acute pancreatitis, the values of the anandamide increased and the value of severe pancreatitis was significantly higher than that of mild pancreatitis. The appearance of CBI rceptors in the glomerulus of the kidney was elevatd only after the induction of severe acute pancreatitis. The local inflammatory changes in the pancreas were not different regardless of the injection of SR141716A. However, the mortality rate was significantly reduce by the injection of SRI41716A. These findings indicate that cannabinoids have an important roll in the deterioration of acute pancreatitis and that the regulation of cannabinoids could be a new therapy for severe acute pancreatitis.