title: Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury.
abstract: The pathological activation of digestive zymogens within the pancreatic acinar cell probably plays a central role in initiating many forms of pancreatitis. To examine the relationship between zymogen activation and acinar cell injury, we investigated the effects of secretagogue treatment on isolated pancreatic acini. Immunofluorescence studies using antibodies to the trypsinogen-activation peptide demonstrated that both CCK (10(-7) M) hyperstimulation and bombesin (10(-5) M) stimulation of isolated acini resulted in trypsinogen processing to trypsin. These treatments also induced the proteolytic processing of procarboxypeptidase A1 to carboxypeptidase A1 (CA1). After CCK hyperstimulation, most CA1 remained in the acinar cell. In contrast, the CA1 generated by bombesin was released from the acinar cell. CCK hyperstimulation of acini was associated with cellular injury, whereas bombesin treatment did not induce injury. These studies suggest that 1) proteolytic zymogen processing occurs within the pancreatic acinar cell and 2) both zymogen activation and the retention of enzymes within the acinar cell may be required to induce injury.
authors.affiliation: Department of Surgery, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516, USA.
authors.forename: T
authors.initials: T
authors.lastname: Grady
authors.forename: M
authors.initials: M
authors.lastname: Mah'Moud
authors.forename: T
authors.initials: T
authors.lastname: Otani
authors.forename: S
authors.initials: S
authors.lastname: Rhee
authors.forename: M M
authors.initials: MM
authors.lastname: Lerch
authors.forename: F S
authors.initials: FS
authors.lastname: Gorelick
mesh_terms: D000818:Animals; D001839:Bombesin / Q000187:drug effects / Q000502:physiology*; D002268:Carboxypeptidases / Q000378:metabolism; D043422:Carboxypeptidases A; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D009842:Oligopeptides; C080396:trypsinogen activation peptide; D002108:Ceruletide; D014362:Trypsinogen; D002766:Cholecystokinin; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D014357:Trypsin; D001839:Bombesin