Role of substance P and bradykinin in acute pancreatitis induced by secretory phospholipase A2

Objectives: Secretory phospholipases A(2) (sPLA(2)s) induce acute pancreatitis when injected into the common bile duct of rats. Substance P via neurokinin 1 (NK-1) receptors and bradykinin via B-2 receptors are described to play important roles in the pathophysiology of acute pancreatitis. This study was undertaken to evaluate the role of substance P and bradykinin in the sPLA(2)-induced pancreatitis. Methods: Rats were submitted to the common bile duct injection of sPLA(2) obtained from Naja mocambique mocambique venom at 300 mu g/kg. At 4 hours thereafter, measurement of pancreatic plasma extravasation, pancreatic and lung myeloperoxidase (MPO), serum amylase, and serum tumor necrosis factor alpha levels were evaluated. Results: Injection of sPLA(2) significantly increased all parameters evaluated. Pretreatment with either the NK-1 receptor antagonist SR140333 or the B-2 receptor antagonist icatibant largely reduced the increased pancreatic plasma extravasation and circulating levels of tumor necrosis factor alpha. Both treatments partly reduced the MPO levels in the pancreas, whereas in the lungs, icatibant was more efficient to reduce the increased MPO levels. In addition, icatibant largely reduced the serum levels of amylase, whereas SR140333 had no significant effect. Conclusions: We concluded that NK-1 and B-2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA(2).