Journal article
The bifunctional rat pancreatic secretory trypsin inhibitor/monitor peptide provides protection against premature activation of pancreatic juice.
- Graf R Pancreatitis Research Laboratory, Department of Surgery, University Hospital, Zürich, Switzerland. rgf@chi.usz.ch
- Klauser S
- Fukuoka SI
- Schiesser M
- Bimmler D
- 2003-05-29
Published in:
- Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. - 2003
Animals
Binding Sites
Binding, Competitive
Cattle
Dose-Response Relationship, Drug
Drug Resistance
Endopeptidases
Intercellular Signaling Peptides and Proteins
Male
Pancreas
Pancreatic Juice
Rats
Rats, Wistar
Receptors, Cell Surface
Trypsin
Trypsin Inhibitor, Kazal Pancreatic
Trypsin Inhibitors
Trypsinogen
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1159/000070729
- PMID 12771515
- Persistent URL
- https://folia.unifr.ch/global/documents/103942
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