title: Trypsinogen activation in rat pancreatic acinar cells hyperstimulated by caerulein.
abstract: Inappropriate trypsinogen activation is discussed as an early intracellular event in the secretagogue-induced model of acute pancreatitis. However, the mechanisms by which trypsinogen is activated are not well characterized. In the present work, trypsinogen activation was studied in intact acinar cells using bis-(CBZ-arginyl)-Rhodamine 110 [(CBZ-Arg)2-Rho 110] as a cell-permeant substrate for trypsin and also independently via the formation of trypsinogen activation peptide (TAP). Preincubation with 10 nM caerulein increased the Rho 110-substrate cleavage more than threefold. This proteolytic activity was fully sensitive to a benzamidine (BA)-type serine protease inhibitor. The appearance of enzymatic activity was paralleled by the formation of TAP. The lack of effect of the high-molecular soybean trypsin inhibitor indicates an intracellular substrate cleavage. The cathepsin B inhibitor CA-074 prevented neither the caerulein-induced formation of TAP nor the (CBZ-Arg)2-Rho 110-cleaving activity. BA inhibited the Rho 110-substrate cleavage and significantly reduced the TAP formation. These results show that trypsinogen activation in caerulein-hyperstimulated acinar cells may occur independently of the activity of cathepsin B. On the contrary, the effect of BA suggests the role of a serine protease in trypsinogen activation.
authors.affiliation: Department of Experimental Surgery, University of Magdeburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Halangk
authors.forename: J
authors.initials: J
authors.lastname: Stürzebecher
authors.forename: R
authors.initials: R
authors.lastname: Matthias
authors.forename: H U
authors.initials: HU
authors.lastname: Schulz
authors.forename: H
authors.initials: H
authors.lastname: Lippert
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D002108:Ceruletide / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: D014361:Trypsin Inhibitors; D002108:Ceruletide; D014362:Trypsinogen; D002401:Cathepsin B