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PubMed1979

Identification and characterization of trypsin, chymotrypsin and elastase inhibitors in porcine serum.

Characterization of the trypsin-, chymotrypsin- and elastase-inhibiting properties of porcine serum was carried out by gel filtration on Ultrogel, AcA 44, and agarose gel electrophoresis with subsequent processing for protease-inhibiting activity. Moreover, by allowing the fractions obtained from gel filtration to react with antibodies to porcine serum protease inhibitors, the specific inhibiting properties of these inhibitor molecules were identified. At least six protease inhibitors were identified and partially characterized in porcine serum. Two alpha 2 -macroglobulins (alpha 2 Mf and alpha 2 Ms), homologues to human alpha 2 -macroglobulin, with slightly different electrophoretic mobilities, were both found to exhibit trypsin, chymotrypsin and elastase inhibiting activity. Alpha 1 -Protease inhibitor (Mr 51 000), a homologue to human alpha 1 -protease inhibitor (alpha 1 -antitrypsin), also showed trypsin-, chymotrypsin- and elastase-inhibiting properties. Inter-alpha-trypsin inhibitor (Mr 162 000 and 129000), a porcine serum counterpart to human inter-alpha-trypsin inhibitor, showed trypsin- and chymo-trypsin-inhibiting properties. In addition, a specific trypsin inhibitor, alpha 2 -antigrypsin (Mr 58 000), and a specific elastase inhibitor, beta-elastase inhibitor, were characterized in porcine serum, and these seem to have no counterparts in human serum.

Animals↗
PubMed1988

Interactions in vitro and in vivo between anionic and cationic porcine trypsin and porcine plasma proteinase inhibitors.

A method for purifying porcine anionic and cationic trypsin is presented. Reaction mixtures with increasing amounts of the two porcine trypsins and porcine serum were studied in vitro to evaluate the relative importance of alpha 1-macroglobulin and alpha 2-macroglobulin as well as alpha 1-proteinase inhibitor in the rapid binding of porcine anionic and cationic trypsin. Porcine cationic trypsin was preferentially bound to alpha 1-macroglobulin, while anionic trypsin exhibited equal binding to both alpha-macroglobulins. Both trypsins were also bound by the alpha 1-proteinase inhibitor but not until alpha 1-macroglobulin approached saturation. Trypsin-alpha-macroglobulin complexes were cleared from plasma with a half-life of 6 min. For trypsin-alpha 1-proteinase inhibitor-complexes the half-life was 120 min. These findings are in accordance with results for other mammalian species, including man.

Animals↗
PubMed1980

The relative values of serum immuno-reactive trypsin concentration and total amylase activity in the diagnosis of mumps, chronic renal failure, and pancreatic disease.

Fasting serum concentrations of trypsin and amylase activity have been compared in 107 subjects, including 18 controls and patients with mumps, acute pancreatitis, chronic pancreatitis, cancer of the pancreas, and chronic renal failure. There was no significant correlation between amylase activity and trypsin concentrations in any of these groups. In all 12 patients with acute pancreatitis and all 16 with chronic renal failure the serum immuno-reactive trypsin concentrations were elevated. Amylase activity was increased in 87% (20 out of 23) of patients with mumps, but only 13% (3 out of 23) had hypertrypsinaemia suggesting subclinical pancreatitis. In 18 patients with chronic pancreatitis low levels of serum trypsin were measured in 11 (61%), reflecting a decrease in pancreatic acinar mass. In contrast, serum amylase was normal or raised in all 18. Subnormal values of the trypsin to amylase ratio was obtained in 15 (83%). Trypsin levels in 20 patients with carcinoma of the pancreas were abnormal in 11 (55%). Six (30%) had abnormal amylase levels. It is concluded that it is more useful to measure the serum trypsin concentration than the amylase activity in the diagnosis of both mumps-pancreatitis and chronic pancreatic disease and that the trypsin to amylase ratio is more sensitive than either enzyme alone in the diagnosis of chronic pancreatitis.

Adult↗
PubMed2004

Evaluation of a colostrum supplement, with or without trypsin inhibitor, and an egg protein milk replacer for dairy calves.

Forty-eight Holstein bull calves were assigned to a 2 x 2 x 2 factorial arrangement in a completely randomized block design. Main effects were colostrum versus a serum-derived colostrum supplement, 0 versus 1 g of trypsin inhibitor added at the initial 2 feedings, and milk replacer containing 0 or 50% CP from whole egg. Calves were bled at 0, 6, 12, 18, and 24 h after birth for determination of serum immunoglobulin (Ig). G. Serum IgG concentrations were lower in calves consuming the colostrum supplement compared with calves consuming colostrum. Apparent efficiency of absorption of IgG was similar. Trypsin inhibitor did not affect IgG concentrations or absorption of IgG. Calves were fed either milk replacer for 28 to 35 d (preweaning phase) and weaned when they consumed 0.7 kg of starter grain for 2 consecutive days. The postweaning phase was from weaning to d 56. Feeding colostrum supplement resulted in higher fecal scores postweaning (1.90 vs. 1.58) and overall (1.85 vs. 1.65) and fewer days medicated preweaning (5.1 vs. 2.2 d) and postweaning (3.9 vs. 1.9 d) and overall (9.0 vs. 4.2 d). Calves were treated for upper respiratory tract infections and diarrhea. Dry matter intake and weaning age were not affected by treatment. Postweaning (1.69 vs. 1.2 kg) and overall (1.22 vs. 1.0 kg), calves that received colostrum and egg milk replacer consumed more dry matter and starter. Postweaning, calves fed colostrum and egg milk replacer had similar or greater body weight and gains compared with calves fed colostrum and milk protein milk replacer. Preweaning, feed efficiency was greater for calves fed colostrum (0.44 vs. 0.34), trypsin inhibitor (0.42 vs. 0.36), and milk protein milk replacer (0.48 vs. 0.30) compared with calves fed colostrum supplement, no trypsin inhibitor, and egg milk replacer, respectively. Trypsin inhibitor increased feed efficiency postweaning. Calves fed trypsin inhibitor and milk protein milk replacer were more efficient preweaning and overall than calves fed trypsin inhibitor and egg milk replacer. Results indicate that the blood derived colostrum supplement did not provide as much IgG as colostrum (4.55 g/L vs. 14.6 g/L, respectively), that feeding 1.0 g of trypsin inhibitor did not enhance serum IgG concentrations, and that the egg milk replacer-fed calves fed colostrum performed nearly as well as calves fed colostrum and the milk protein milk replacer.

Absorption↗
PubMed2000

Marked increase of trypsin(ogen) in serum of linitis plastica (gastric cancer, borrmann 4) patients.

Linitis plastica, or Borrmann 4 gastric cancer, shows very poor prognosis, and the reason has not been understood. In the present study, we examined serum levels of trypsin(ogen) in 44 gastric cancer patients, including 17 early gastric cancer, 18 non-Borrmann 4 advanced gastric cancer, and 9 Borrmann 4 gastric cancer, by using the RIA gnost Trypsin kit (Hoechst Japan, Tokyo, Japan), which was expected to detect trypsin-1, trypsin-2, trypsinogen-1, and trypsinogen-2 in sera. The trypsin(ogen) concentration was much higher in the patients with linitis plastica than in the other gross types of gastric cancer. Hypertrypsinemia was identified in approximately 60% of advanced gastric cancer cases. Lymph node involvement, liver metastasis, or poorly differentiated adenocarcinoma is an important factor of hypertrypsinemia. The serum trypsin(ogen) level in linitis plastica patients was 3484.4 +/- 2319.7 ng/ml (mean +/- SD), which was significantly higher not only than that of the early gastric cancer (384.1 +/- 92.1) but also the stage IV gastric cancer patients (578 +/- 440.4), excluding those with linitis plastica. The elevated serum trypsinogen level in linitis plastica patients may be related to the malignant behavior of this type of cancer cell. Serum trypsin(ogen) of linitis plastica shows significantly higher concentrations than do the other types of advanced gastric cancer. Therefore, serum concentration of trypsin(ogen) might be a good marker of gastric cancer of linitis plastica.

Humans↗
PubMed2000

Electrostatics of mesophilic and psychrophilic trypsin isoenzymes: qualitative evaluation of electrostatic differences at the substrate binding site.

A qualitative evaluation of electrostatic features of the substrate binding region of seven isoenzymes of trypsin has been performed by using the continuum electrostatic model for the solution of the Poisson-Boltzmann equation. The sources of the electrostatic differences among the trypsins have been sought by comparative calculations on selective charges: all charges, conserved charges, partial charges, unique cold trypsin charges, and a number of charge mutations. As expected, most of the negative potential at the S(1) region of all trypsins is generated from Asp(189), but the potential varies significantly among the seven trypsin isoenzymes. The three cold active enzymes included in this study possess a notably lower potential at and around the S(1)-pocket compared with the warm active counterparts; this finding may be the main contribution to the increased binding affinity. The source of the differences are nonconserved charged residues outside the specificity pocket, producing electric fields at the S(1)-pocket that are different in both sign and magnitude. The surface charges of the mesophilic trypsins generally induce the S(1) pocket positively, whereas surface charges of the cold trypsins produce a negative electric field of this region. Calculations on mutants, where charged amino acids were substituted between the trypsins, showed that mutations in Loop2 (residues 221B and 224) and residue 175, in particular, were responsible for the low potential of the cold enzymes.

Amino Acid Sequence↗
PubMedDate not supplied

[Immobilization of trypsin on polyurethane matrix].

A method is developed to bind trypsin with the polyurethane matrix. At the first stage the reaction between trypsin and toluylendiisocyanate (TD1) was performed. At the second stage polyisocyanate obtained on the base of TDI-trypsin was sewn with polyoxypropylene glycol with a molecular weight of 1500. 2,4,6-Tris(dimethylaminomethyl)phenol served as an accelerator of the reaction. The polymer obtained is fine-porous and high-elastic. The chemical interaction of trypsin with the polymer is confirmed by the method of IR-spectroscopy and a decrease in the amount of free isocyanate groups. It is shown that the enzymic activity of trypsin chemically bound with the polymer is preserved at a room temperature for several months. When the polymeric net is formed from macrodiisocyanate in the presence of trypsin under conditions when the chemical interaction between the polymer and enzyme activity is also preserved, its value in this case being dependent on the relative content of the enzyme in the polymer -- it is higher in the case when the relative content of the enzyme is less, that may indicate the role of the polymer as a heterogenic cocatalyst or activator. The value of the proteolytic activity of the polymer with the chemically added trypsin is practically constant with its washing off in the column for 24h with 0,05 M veronal buffer whereas under these conditions the polymer with "free" trypsin loses completely the enzymic activity.

Binding Sites↗
PubMed1976

Initiation of lung cell proliferation by trypsin.

The ability of trypsin to initiate DNA synthesis in alveolar epithelial cells of mice was tested by introducing solutions containing trypsin into the lung. The concentrations tested ranged from 0.01 to 1.0 mg. per ml., the site of action was identified by adding colloidal carbon as a tracer, and chromosomal DNA synthesis was detected by autoradiography on the basis of strong nuclear incorporation of tritiated thymidine. In the above concentration range trypsin did not cause cell necrosis, general fragmentation of cell processes, or loss of mechanical contact at epithelial cell junctions. Edema and focal acute inflammation were apparent at concentrations of trypsin above 0.1 mg. per ml. In the alveolar epithelium maximal labeling was seen 2 days after treatment with 0.5 mg. per ml. of trypsin. At this time electron microscope autoradiography covering two "S" periods showed that one-third of the type II cells were labeled. No labeled type I cells were seen. Trypsin at levels less than 0.1 mg. per ml. did not increase the frequency of labeled type II cells above that of the saline-colloidal ink solution alone. Mesothelial cells lining the lung were stimulated by trypsin (0.5 mg.) given intrapleurally. The frequency of mesothelial cell labeling peaked at 2 days with a labeling index for a single tritiated thymidine pulse of 18 per cent. Neither alveolar type II cells nor mesothelial cells showed increased labeling when trypsin inactivated by diisopropyl fluorophosphate was used.

Animals↗
PubMed1992

Identification of alpha 2-macroglobulin conformational intermediates by electron microscopy and image analysis. Comparison of alpha 2-macroglobulin-thrombin and alpha 2-macroglobulin reacted with cis-dichlorodiammineplatinum(II) and trypsin.

Human alpha 2-macroglobulin (alpha 2M) exists in two well defined, highly distinct conformations and in less well described intermediate conformations. In this study, previously characterized reactions were used to partially or completely transform the conformation of alpha 2M. Electron micrographs of each preparation were subjected to image analysis. Ternary alpha 2M-trypsin (2 mol of trypsin/mol of alpha 2M) was analyzed as a control for the fully transformed state. Correspondence analysis (CORAN) and hierarchical ascendant classification (HAC) generated five image clusters from 330 aligned alpha 2M-trypsin complexes. Average images of each cluster resembled the letter "H" with four nearly equivalent lateral arms. Abnormally shaped lateral arms were not demonstrated by HAC, using a variety of factor sets. In a native polyacrylamide gel electrophoresis system, alpha 2M-thrombin migrated in a diffuse band partially behind alpha 2M-trypsin, suggesting conformational heterogeneity. CORAN and HAC of 733 alpha 2M-thrombin complexes identified two neighboring clusters, the average images of which showed an H-like structure in which one arm was replaced by a globular stain-excluding body. The two alpha 2M-thrombin clusters included 125 images (17.1% of image population). The complete absence of atypical lateral arm structure in the alpha 2M-trypsin clusters suggests that this variation is not the result of orientation or staining artifact. Native alpha 2M was reacted with cis-dichlorodiammineplatinum(II) and then with trypsin to form alpha 2M-Pt-trypsin, a preparation that includes partially transformed alpha 2M structures. CORAN and HAC of 580 alpha 2M-Pt-trypsin complexes generated five clusters, the average images of which showed atypical lateral arm structure equivalent to that demonstrated with alpha 2M-thrombin. The five alpha 2M-Pt-trypsin clusters accounted for 15.2% of the image population. These studies suggest that alpha 2M conformational change intermediates demonstrate common structural characteristics, permitting an elucidation of the steps involved in this complex transformation.

Cisplatin↗
PubMed1989

Trypsin-binding immunoglobulin G and associated antigen in cystic fibrosis.

Trypsin-binding immunoglobulin G (TBIgG) is found in the sera of a high proportion of patients with cystic fibrosis. We previously reported that TBIgG preferentially binds human cationic trypsin rather than trypsin from other animal species. Binding affinity is enhanced by complex formation with bovine pancreatic trypsin inhibitor, which is known to induce characteristic conformational modifications in the active site region of the trypsin molecule. To identify the human trypsin-like antigen associated with TBIgG, we have studied the effects of conformational changes of cationic trypsin induced by limited proteolysis based on competitive binding studies. It is shown that the most likely TBIgG-related self-antigen is an 11,000-dalton fragment that is a cleavage product of the complex formed by trypsin and alpha 1-protease inhibitor. This result emphasizes the occurrence of circulating trypsinogen activation and is interpreted to be a consequence of the protease-antiprotease imbalance, which has been well documented by previous investigators in cystic fibrosis and also in other lung diseases associated with an inflammatory state.

Binding, Competitive↗
PubMed1988

Functional differentiation of cyclooxygenase and peroxidase activities of prostaglandin synthase by trypsin treatment. Possible location of a prosthetic heme binding site.

Treatment of prostaglandin (PG)H synthase purified from ram seminal vesicle microsomes with trypsin cleaves the 70-kDa subunits into 33- and 38-kDa fragments (Chen, Y.-N. P., Bienkowski, M. J., and Marnett, L. J. (1987) J. Biol. Chem. 262, 16892-16899). In contrast to a minimal decrease in cyclooxygenase activity, peroxidase activity declines rapidly following trypsin treatment. The time course for loss of guaiacol peroxidase activity corresponds closely to the time course for protein cleavage. The ability of trypsin-treated enzyme to support catalytic reduction of 5-phenyl-4-pentenyl-1-hydroperoxide in the presence of reducing substrates is significantly reduced. The products of metabolism of 10-hydroperoxy-8,12-octadecadienoic acid indicate that trypsin-treated enzyme catalyzes homolytic scission of the hydroperoxide bond in contrast to the heterolytic scission catalyzed by intact enzyme. Spectrophotometric titrations of hematin addition to trypsin-treated PGH synthase indicate approximately a 50% reduction in heme binding. These observations suggest that trypsin treatment of PGH synthase decreases the ability of the protein to bind prosthetic heme at a site that controls peroxidase activity. Comparison of the N-terminal sequence of the 38-kDa fragment of trypsin-treated PGH synthase to the amino acid sequence of the intact protein indicates that cleavage occurs between Arg253 and Gly254. Based on literature precedents and the results of the present investigations, we propose that the heme prosthetic group that controls the peroxidase activity of PGH synthase binds to the His residue of the sequence His250-Tyr251-Pro252-Arg253 located immediately adjacent to the trypsin cleavage site.

Animals↗
PubMed1986

Autolysis of beta-trypsin at pH 3.0.

Bovine beta-trypsin was prepared from commercial crystalline trypsin by SP-Sephadex equilibrium chromatography (D.D. Schroeder and E. Shaw, Journal of Biological Chemistry, 243: 2943-2949, 1968) and by a modification which included 0.1 M NaCl in the eluting buffer to reduce the buffer volume (time) required. SDS-PAGE analysis indicated that beta-trypsin prepared by both methods contained appreciable amounts of alpha-trypsin. The following relative amounts of alpha-trypsin were detected at each step of the process: 4.4% eluted from the column into pH 3.0 buffer; 10.7% after concentration on SP-Sephadex; 14.9% after desalting at pH 3.0; 16.1% after lyophilization. These data show that even at pH 3.0, a condition under which trypsin is believed to be inactive, and which is employed for preparation and storage of trypsin solutions, appreciable partial proteolysis can occur to generate the two-chain alpha form from beta-trypsin.

Chromatography, Ion Exchange↗
PubMed1976

Trypsin-sensitive photosynthetic activities in chloroplast membranes from Chlamydomonas reinhardi, y-1.

Location of electron transport chain components in chloroplast membranes of chlamydomonas reinhardi, y-1 was investigated by use of proteolytic digestion with soluble or insolubilized trypsin. Digestion of intact membrane vesicles with soluble trypsin inactivates the water-splitting system, the 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition site of Photosystem II, the electron transport between the two photosystems as well as the ferredoxin NADP reductase. Reduction of NADP with artificial electron donors for Photosystem I could be restored, however, by addition of purified reductase to trypsin-digested membranes. Electron transfer activities of Photosystems I and II reaction centers were resistant to trypsin digestion either from outside or from within the thylakoids when active trypsin was trapped inside the membrane vesicles by sonication and digestion carried out in the presence of trypsin inhibitor added from outside. In the latter case, the water-splitting system was also found to be resistant to digestion. Polyacrylamide-bound insolubilized trypsin inactivated only the ferredoxin NADP reductase. Photosynthetically active membranes obtained at different stages of development showed a basically similar behavior toward trypsin.

Cell Membrane↗
PubMed1994

Nylon-6 cylinders and a sponge-like derivative as supports for immobilizing trypsin.

1. Two types of nylon-6 supports (small cylinders and a sponge-like derivative) were prepared for immobilizing enzymes. Nylon-6 beads were solubilized by immersion in 80% formic acid and then reprecipitated using two different types of non-solvent solutions (distilled water or a 1:1 acetone:water solution) giving rise to a sponge-like derivative and to a colloidal suspension, respectively. The latter was molded into a thin thread which was cut into small cylinders. 2. Trypsin (EC 3.4.21.4) was covalently bound to glutaraldehyde-activated nylon-6 cylinders as well as to the sponge-like derivative. The maximum (100%) apparent initial enzymatic activity was found for the trypsin bound to small cylinders, while the initial activity of trypsin bound to the sponge-like material was 61% in comparison with that of trypsin-small cylinders, under the same conditions of enzyme immobilization reaction (1 g of nylon support and 5 ml of 1.3 mg/ml trypsin in 0.1 M sodium phosphate buffer, pH 8.5, at 10 degrees C for 18 h) and of enzymatic reaction (1 g of trypsin-nylon in a batch reactor, 2 ml of 0.7% w/v azocasein solution in 50 mM borate buffer, pH 8.5, at 37 degrees C, with shaking, for 1 h). However, the decrease of activity after enzyme immobilization was more conspicuous for the trypsin-small cylinders than for the trypsin-sponge. The former retained approximately 25% of its initial activity, while the latter retained approximately 67% of its initial activity, after seven cycles of utilization for 1 h, pH 8.5, at 37 degrees C and 8 days of storage, pH 8.5, at 4 degrees C in the presence of azocasein. 3. Scanning electron microscopy was performed to visualize the surface of the support after each step of the immobilization process. The electron micrographs show that the two types of nylon supports had a rough surface, which became rougher and full of craters after treatment with 5 N HCl. On the other hand, the partially hydrolyzed nylon surface acquired the appearance of Swiss cheese after treatment with 2.5% glutaraldehyde. After reaction with the enzyme molecules the surface became rougher again.

Caprolactam↗
PubMed1994

Chymotrypsin and trypsin sensitivities of avian reoviruses.

Experiments were undertaken to examine the chymotrypsin sensitivity and trypsin sensitivity of 13 avian reoviruses, and to determine if there was any correlation with pathogenicity of some chicken reoviruses. A wide variation in the degree of sensitivity of avian reoviruses to chymotrypsin and trypsin was observed. Overall, the infectivity of the 13 avian reoviruses for Vero cells was markedly reduced by treatment with 0.01% chymotrypsin (the lowest concentration tested) while 0.5% trypsin significantly reduced the infectivity of 9 of 13 strains. Comparison of four avian reoviruses, three resistant and one sensitive to trypsin, for pathogenicity in day old chicks following oral inoculation showed the strains that were resistant to trypsin to be more pathogenic. Tenosynovitis and virus persistence in intestines, liver, heart and hock joint tissues occurred only in chickens inoculated with the trypsin resistant strains. It is concluded that the degree of sensitivity to chymotrypsin and trypsin among avian reoviruses is heterogenous. Sensitivity to trypsin influenced the development of tenosynovitis based on microscopic lesions and virus persistence in tissues.

Animals↗
PubMed1993

Trypsin digestion increases Na(+)-H+ exchange rates in native rabbit brush border membrane.

Experiments were designed to examine the effects of trypsin-mediated proteolysis on the activity of the rabbit renal brush border membrane Na(+)-H+ exchanger. Incubation of brush border membrane vesicles with trypsin resulted in a concentration and time-dependent change in proton gradient-stimulated sodium uptake. Extensive trypsin digestion resulted in a marked decrease in the activity of the transporter. By contrast, limited trypsin digestion resulted in a significant increase in proton gradient-stimulated, amiloride-inhibitable sodium uptake. Sodium-dependent proton efflux was also significantly increased by limited trypsin digestion. The passive permeability of the vesicles to sodium and protons, and the sodium-dependent and sodium-independent uptake of glucose were not affected by limited trypsin digestion. These data indicate that limited trypsin digestion increases the activity of the renal brush border membrane Na(+)-H+ exchanger. It is suggested that the renal Na(+)-H+ exchanger contains one or more inhibitory components or sites which are sensitive to inactivation by limited trypsin-mediated proteolysis.

Amiloride↗
PubMed1986

Localization of pancreatic enzyme secretion-stimulating activity and trypsin inhibitory activity in zymogen granule of the rat pancreas.

The intracellular localization of pancreatic enzyme secretion-stimulating activity in rat pancreas was investigated. We found and purified a pancreatic enzyme secretion-stimulating peptide from rat bile/pancreatic juice. The peptide is trypsin-sensitive (showing temporary trypsin inhibitory activity), and it is hypothesized that it acts as a trypsin-sensitive mediator in the feedback regulation of diet-induced pancreatic enzyme secretion. The zymogen granule fraction was purified 5-fold by ultracentrifugation by the Percoll density gradient method. The purity of the zymogen granule fraction was determined from the specific amylase activity and electron microscopic morphology. The specific enzyme activities of amylase and trypsin and the trypsin inhibitory activity increased in parallel during the purification, and the pancreatic enzyme secretion-stimulating activity was also localized in the zymogen granule fraction. These results suggest that the pancreatic enzyme secretion-stimulating peptide originates from the acinar cells, and that it is secreted through exocytosis of zymogen granules into the small intestine, its ratio to trypsin thus remaining constant. This idea supports our hypothesis that the stimulating peptide acts as a mediator for the feedback regulation of pancreatic enzyme secretion by trypsin.

Amylases↗
PubMed2003

The bifunctional rat pancreatic secretory trypsin inhibitor/monitor peptide provides protection against premature activation of pancreatic juice.

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.

Animals↗