PMID: 9436869Jan 22, 1998Paper

Inhibition of cathepsin B does not affect the intracellular activation of trypsinogen by cerulein hyperstimulation in isolated rat pancreatic acinar cells

Pancreas
H Klonowski-StumpeC Niederau

Abstract

Activation of trypsinogen is thought to trigger the autodigestive process in acute pancreatitis. The lysosomal enzyme cathepsin B was suggested to cause the activation of trypsinogen because it is known that cathepsin B is able to activate trypsinogen in special circumstances and that lysosomal and digestive enzymes are colocalized within intracellular vacuoles in the early stage of pancreatitis. As yet this hypothesis has been difficult to prove because activated trypsin is difficult to quantify in pancreatitis by conventional enzymatic measurements. We therefore employed an ELISA for trypsin activating peptide (TAP), which is a small peptide cleaved during the activation of trypsinogen and can be determined reliably. Supraphysiological concentrations of cerulein (1 nM-1 microM) resulted in a marked increase in TAP in freshly isolated pancreatic acinar cells, indicating activation of trypsinogen. This activation as determined by the TAP increase was significantly reduced by the serine protease inhibitor Fut-175 but not by the cathepsin B inhibitors E-64 and NCO-700. The concentrations of NCO-700 and E-64 abolished the cathepsin B activity of pancreatic acinar cells but did not significantly reduce the trypsin activity (after e...Continue Reading

Citations

Jan 6, 2007·Digestive Diseases and Sciences·David C Whitcomb, Mark E Lowe
Sep 2, 1999·The Surgical Clinics of North America·S Karne, F S Gorelick
Jun 30, 2000·Journal of Clinical Gastroenterology·G H Sakorafas, A G Tsiotou
Oct 25, 2003·Pancreas·Markus M LerchBurkhard Krüger
Sep 21, 2000·The Journal of Clinical Investigation·W HalangkJ Deussing
Nov 6, 2004·Gastroenterology Clinics of North America·Walter Halangk, Markus M Lerch
Mar 8, 2005·Clinics in Laboratory Medicine·Walter Halangk, Markus M Lerch
Jun 27, 2019·Scientific Reports·Alexandra DemcsákMiklós Sahin-Tóth
Nov 14, 1998·The American Journal of Physiology·T OtaniF S Gorelick

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