THE EFFECTS OF TRYPSIN ON PANCREATIC PAR-2 RECEPTORS

Abstract

Background: The pathophysiology of acute pancreatitis is associated with the hypersecretion of the pancreas. Under these conditions, premature activation of trypsin has been described in acinar cells, which can activate protease-activated receptor-2 (PAR-2) and trigger cellular responses. However, no data is available about the localization and activation of PAR-2 receptors on pancreatic duct cells. In this study, we investigated the expression of PAR-2 and the effects of trypsin (PAR-2 receptor agonist) and PAR-2-activating peptide (PAR2-AP) on intracellular calcium of pancreatic duct cells in the guinea pig pancreas. Methods: Intracellular calcium was measured on isolated intra/interlobular microperfused pancreatic ducts from guinea pig pancreas. Immunohistochemical localization of PAR-2 was performed by immunoperoxidase staining of the pancreatic tissue. Results: Trypsin and PAR2-AP, even at low concentrations, activated Ca2+signaling from the basal membrane and trypsin from the luminal membrane of the duct cells. The soybean trypsin inhibitor and a calcium chelator BAPTA-AM totally blocked the effect of trypsin on intracellular calcium, while Ca2+free external solution did not prevent the effect. PAR-2 is expressed on the luminal membrane of intralobular but not interlobular ducts, where expression of the receptor was not detected. Conclusion: Our results suggest that PAR-2 receptors may be the targets by which pancreatic duct cells are activated at the early stage of acute pancreatitis. The role of the receptors and their activation on pancreatic ductal epithelia during the inflammation of the pancreatic tissue still needs to be investigated. This work was supported by OTKA, MTA, OM.