Acute pancreatitis: proteinase-activated receptor-2 as Dr. Jekyll and Mr. Hyde

"Proteinase-activated" receptor-2 (PAR-2) is a G protein-coupled transmembrane receptor with seven transmembrane domains activated by trypsin. It has been shown in the pancreatic tissue that PAR-2 is involved in duct/acinary cells secretion, arterial tonus regulation and capillary liquid content turnover under physiological conditions. These above mentioned structures play an important role during the development of acute pancreatitis and are profoundly influenced by a high concentration of trypsin enzyme after its secretion into the interstitial tissue from the basolateral aspect of acinar cells. Among the other factors, it is the increase of interstitial trypsin concentration followed rapidly by PAR-2 action on pancreatic vascular smooth muscle cells that initiates ischemic changes in pancreatic parenchyma and that finally leads to necrosis of the pancreas. Consequent reperfusion perpetuates changes leading to the acute pancreatitis development. On the contrary, PAR-2 action on both exocrine and duct structures seems to play locally a protective role during acute pancreatitis development. Moreover, PAR-2 action is not confined to the pancreas but it contributes to the systemic vascular endothelium and immune cell activation that triggers the systemic inflammatory response syndrome (SIRS) contributing to an early high mortality rate in severe disease.