Role of substance P and bradykinin in acute pancreatitis induced by secretory phospholipase A2.
OBJECTIVE
Secretory phospholipases A2 (sPLA2s) induce acute pancreatitis when injected into the common bile duct of rats. Substance P via neurokinin 1 (NK-1) receptors and bradykinin via B2 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 sPLA2-induced pancreatitis.


METHODS
Rats were submitted to the common bile duct injection of sPLA2 obtained from Naja mocambique mocambique venom at 300 microg/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 sPLA2 significantly increased all parameters evaluated. Pretreatment with either the NK-1 receptor antagonist SR140333 or the B2 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 B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2.
Camargo
Enilton A
EA
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Ferreira
Tatiane
T
Ribela
Maria Teresa C P
MT
de Nucci
Gilberto
G
Landucci
Elen C T
EC
Antunes
Edson
E
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D004195:Disease Models, Animal; D008168:Lung / Q000201:enzymology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D054497:Phospholipases A2, Secretory; D010880:Piperidines / Q000494:pharmacology; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D065094:Bradykinin B2 Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D043782:Receptor, Bradykinin B2; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; C085215:SR 140333; D013373:Substance P; C065679:icatibant; D009195:Peroxidase; D054497:Phospholipases A2, Secretory; D000681:Amylases; D001920:Bradykinin