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The Bifunctional Rat Pancreatic Secretory Trypsin Inhibitor/Monitor Peptide Provides Protection against Premature Activation of Pancreatic Juice.

Authors: Graf, R  Klauser, S  Fukuoka, SI  Schiesser, M  Bimmler, D 
Citation: Graf R, etal., Pancreatology 2003;3(3):195-206.
Pubmed: (View Article at PubMed) PMID:12771515
DOI: Full-text: DOI:10.1159/000070729

BACKGROUND: In the rat, two forms of the pancreatic secretory trypsin inhibitor, PSTI-I and PSTI-II, are secreted into pancreatic juice. It is assumed that their role is to protect the pancreas from premature activation of the protease-rich pancreatic juice. In the small intestine, PSTI-I, also called 'monitor peptide', is thought to have a different role: PSTI-I competes with protein for activated trypsin. In the presence of a protein-rich meal, free PSTI induces a release of cholecystokinine from the intestine. METHODS: To investigate whether its role as monitor peptide is compatible with the inhibitory, protective function in the pancreas, PSTI-I was chemically synthesized and then renatured. RESULTS: The peptide was almost completely trypsin resistant and exhibited a dose-dependent inhibitory activity to bovine and partially purified rat trypsin. Furthermore, experiments with trypsin- and endopeptidase-activated pancreatic juice demonstrated that its inhibitory capacity was sufficient to prevent premature activation. Binding studies of (125)I-labeled PSTI-I with the putative intestinal receptor using isolated membranes indicated the presence of high-affinity binding sites (k(d) = 5 x 10(-8)M). Binding of PSTI-I could be competed with excess PSTI-I or trypsin. In a biological assay system, injections of PSTI-I displayed monitor peptide activity by inducing a dose-dependent trypsinogen release from the pancreas. CONCLUSION: Our experiments support a dual function of PSTI-I: monitoring protein in the gut due to its 'moderate' affinity for trypsin and a protective role in the pancreas.

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CRRD Object Information
CRRD ID: 724699
Created: 2003-10-19
Species: All species
Last Modified: 2003-10-19
Status: ACTIVE



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