Z Gastroenterol 2006; 44 - A49
DOI: 10.1055/s-2006-943415

The effects of trypsin on pancreatic ductal epithelia

I Ignáth 1, V Venglovecz 1, B Ózsvári 1, Z Ifj Rakonczay 1, T Takács 1, J Lonovics 1, K Borka 2, Z Schaff 2, A Tóth 3, A Varró 3, M Sahin-Tóth 4, P Hegyi 1
  • 1First Department of Medicine, University of Szeged, Szeged, Hungary
  • 22nd Department of Pathology, Semmelweis University, Budapest, Hungary
  • 3Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary
  • 4Department of Molecular and Cell Biology, Goldman School of Dental Medicine, Boston University, Boston, Mass., USA

Background: The pathophysiology of acute pancreatitis is associated with pancreatic hypersecretion in the early stages of the disease. Under these conditions, premature activation of trypsinogen has been described in acinar cells, which can activate protease-activated receptor-2 (PAR-2) and trigger cellular responses. However, no data is available on the localization and activation of PAR-2 in pancreatic duct cells.

The aim of this study was to investigate the expression of PAR-2 and the effects of trypsin and PAR-2-activating peptide (PAR2-AP) on intracellular Ca2+ levels of guinea pig pancreatic duct cells.

Methods: Intracellular Ca2+ concentration was measured on isolated intra/interlobular microperfused pancreatic ducts. Immunohistochemical localization of PAR-2 was performed by immunoperoxidase staining of guinea pig pancreatic tissue.

Results: Trypsin and PAR2-AP, even at low concentrations, activated Ca2+ signaling from the basolateral membrane and trypsin from the luminal membrane of the duct cells. Trypsin inhibitor and the Ca2+ chelator BAPTA-AM totally blocked the effect of trypsin on intracellular Ca2+, while a Ca2+-free external solution did not prevent the effect. PAR-2 is expressed on the luminal membrane of intralobular ducts.

Conclusion: Our results suggest that PAR-2 may be the target by which pancreatic duct cells are activated. The role of the receptors and their activation in pancreatic epithelia during the inflammation of the pancreatic tissue needs further investigation. This work was supported by OTKA, MTA, OM.