title: The role of trypsin, trypsin inhibitor, and trypsin receptor in the onset and aggravation of pancreatitis.
abstract: Trypsin activity is properly suppressed in the pancreatic acinar cells under normal conditions. A small amount of trypsinogen is converted to active trypsin and inactivated by pancreatic secretory trypsin inhibitor (PSTI), thereby preventing damage to pancreatic acinar cells as a first line of defense. However, if trypsin activation (due to excessive stimulation of pancreatic acinar cells) exceeds the capacity of PSTI, a subsequent cascade of events leads to the activation of various proteases that damage cells. This can be interpreted as the main causative event of pancreatitis onset. Trypsin produced in and secreted from the pancreatic acinar cells activates protease activated receptor-2 (PAR-2), which is present at high densities on the luminal surfaces of pancreatic acinar cells and duct cells. Results of PAR-2 activation are the production of cytokines and the regulation of exocrine function via a negative feedback loop. Thus, the actions of trypsin, trypsin inhibitor (PSTI), and trypsin receptor (PAR-2) in the pancreas are strongly interconnected.
authors.affiliation: Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirota
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohmuraya
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D006801:Humans; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014361:Trypsin Inhibitors / Q000378:metabolism*; D014362:Trypsinogen / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D044464:Receptor, PAR-2; C486642:SPINK1 protein, human; D014361:Trypsin Inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; D004247:DNA; D014357:Trypsin