Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kallikrein (EC 3.4.21.8) was purified from rat stomach by column chromatography on p-aminobenzamidine-Sepharose, DEAE-Sephadex A-50 and Sephadex G-150 and by isoelectric focusing, measuring its activities to hydrolyse L-prolyl-L-phenylalanyl-L-arginine-4-methyl-coumaryl-7-amide and to release kinin from heat-treated rat plasma. the purified stomach kallikrein showed a single band on polyacrylamide gel electrophoresis at pH 7.0. Its molecular weight was calculated to be 29 000 by gel-filtration on a column of Sephadex G-50. The kallikrein was stable between pH 6-11 and hydrolyzed L-prolyl-L-phenylalanyl-L-arginine-4-methyl-coumaryl-7-amide optimally at pH 11.0. The L-prolyl-L-phenylalanyl-L-arginine-4-methyl-coumaryl-7-amide hydrolyzing activity of rat stomach kallikrein was inhibited by diisopropyl fluorophosphate and Trasylol, but not by trypsin inhibitors from soybean, lima bean and ovomucoid. These properties of rat stomach kallikrein are different from those of partially purified rat plasma kallikrein, but similar to those of glandular kallikreins from other species. From these results, it was concluded that kallikrein is present in rat stomach and that it can be classified as a glandular kallikrein.
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PMID:Purification and properties of rat stomach kallikrein. 615 23

Access to the active site of alpha 2-macroglobulin bound proteinases by macromolecular substrates and inhibitors is likely to be influenced by steric favourability and flexibility, as well as by molecular size. Hydrolysis of pure porcine cholecystokinin-pancreozymin 39, a flexible single chain peptide, by alpha 2-macroglobulin-trypsin complex resulted in a rapid up to 6-fold increase in cholecystokinin bioactivity; alpha 2-macroglobulin-trypsin rapidly abolished the bioactivity of endogenous parathormone in human plasma. Inhibition of both reactions was completed by low concentrations of antipain and leupeptin; Trasylol (aprotinin), a single chain peptide with three disulphide bonds, was an ineffective inhibitor even in massive molar excess. These findings may provide an explanation for the disordered calcium homeostasis in severe acute pancreatitis and for the failure of Trasylol to reduce mortality; they suggest that sterically favourable low molecular weight inhibitors may provide effective specific chemotherapy for the disease.
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PMID:Cleavage of peptide hormones by alpha 2-macroglobulin-trypsin complex and its relation to the pathogenesis and chemotherapy of acute pancreatitis. 616 93

The release in dog plasma of bradykinin in an experimental model in vitro and in vivo secondary to the addition of increasing amounts of trypsin was studied. The release was correlated with the degree of saturation of the plasma protease inhibitors, alpha 2-macroglobulin and alpha 1-antitrypsin, without and in the presence of Trasylol. There was a good correlation between the saturation of alpha 2-macroglobulin with trypsin and the release of bradykinin. A simultaneous fall in blood pressure was seen in the in vivo experiments. alpha 1-Antitrypsin was unable to block this tryptic activity in the absence of free alpha 2-macroglobulin. In the presence of Trasylol, the saturation of alpha 2-macroglobulin was not followed by any significant kinin liberation and the blood pressure remained stable.
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PMID:Influence of plasma protease inhibitors and Trasylol on trypsin-induced bradykinin-release in vitro and in vivo. Protease inhibitors and trypsin-induced bradykinin release. 616 77

An investigation was performed to study the interaction of Trasylol with both trypsin-pancreatic secretory trypsin inhibitor (PSTI) and alpha 2-macroglobulin (alpha 2-M)-trypsin-PSTI complexes. Trasylol was readily able to displace immunogenic PSTI from a complex with trypsin in vitro. A similar scale of displacement of PSTI by Trasylol from alpha 2-M-trypsin-PSTI complexes could not be demonstrated. Using complexes manufactured in vitro with 125I-labelled PSTI, we found that only a small percentage of the PSTI label could be liberated, even when presented with amounts of Trasylol in a 10-molar excess to the PSTI.
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PMID:Studies on the interaction of Trasylol (aprotinin) with trypsin-pancreatic secretory trypsin inhibitor (PSTI) complexes and with alpha 2-macroglobulin-trypsin-PSTI-complexes. 617 56

It has been reported that polyclonal B cell stimulation results in formation of autoantibodies and immune complexes. We have previously reported that a polyclonal B cell activator (PBA) associated with alpha 2-macroglobulin (alpha 2M) is present in the serum of patients with rheumatoid arthritis and related diseases. Here we studied the possibility that patient alpha 2M (Pt-alpha 2M) carries a trypsin-like protease responsible for the PBA activity. This activity was determined by the Ig-turnover assay developed in our laboratories. The small molecular weight protease inhibitors, aprotinin (Trasylol, Bayer) and phenylmethylsulfonylfluoride (PMSF), and the large molecular weight soybean trypsin inhibitor (SBTI) were used. These inhibitors did not affect the PBA activity of dextran sulfate of LPS. However, as expected, trypsin had a PBA-activity which was blocked by all of the above mentioned inhibitors. A trypsin-normal alpha 2M complex (Tr-N alpha 2M) and PBA activity which was inhibited by PMSF or aprotinin but not by SBTI. The PBA associated with Pt-alpha 2M was also inhibited by PMSF or aprotinin but not by SBTI. Moreover, the Tr-N alpha 2M complex and the Pt-alpha 2M, but not that from normal donors, had esterase activity for p-toluenesulfonyl-L-argininemethyl ester. These data suggest a similarity between the Pt-alpha 2M and Tr-N alpha 2M complex. Thus, we concluded that the esterolytic activity is sufficient for PBA activity, that Pt-alpha 2M has esterolytic activity and that this PBA activity can be blocked by small molecular weight protease inhibitors.
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PMID:The effect of protease inhibitors on the polyclonal B cell activator from the serum of patients with rheumatoid arthritis. 617 49

We examined the role of proteases in mediating lung vascular injury after acute hemorrhagic pancreatitis. Studies were made in sheep in which pulmonary lymph was collected for assessment of the changes in transvascular fluid and protein exchange. The induction of pancreatitis by injection of trypsin and sodium taurocholate into the pancreas resulted in increases in pulmonary lymph flow and transvascular protein clearance (lymph flow x lymph-to-plasma protein concentration ratio). The pulmonary vascular pressures did not change significantly after pancreatitis, indicating that the increases in pulmonary lymph flow and protein clearance were due to increased pulmonary endothelial permeability. The response to pancreatitis was also characterized by decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was a common morphologic feature in this group. In another group, an intravenous infusion of trypsin, which produced decreases in antiprotease activity comparable to those observed after pancreatitis, also resulted in increases in pulmonary lymph flow and transvascular protein clearance. These increases in lymph fluxes were comparable to those observed after pancreatitis and were also associated with decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was evident in this group upon histologic examination. In a third group, pretreatment with Trasylol prevented the increases in pulmonary lymph flow and transvascular protein clearance after pancreatitis, suggesting that the pancreatitis-induced pulmonary vascular injury is the result of the release of proteases. The results indicate a common pulmonary vascular response to acute pancreatitis and trypsin infusion. The release of proteases into the circulation after acute pancreatitis may be the initiating event mediating the pulmonary vascular injury.
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PMID:Increased lung vascular permeability after pancreatitis and trypsin infusion. 618 92

Cleavage of native C3 in human serum following the addition of increasing amounts of human cationic trypsin was studied using an in vitro model. The cleavage was correlated with the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-antitrypsin, and also with varying amounts of aprotinin (Trasylol). When alpha 2-macroglobulin reached 70% saturation, there was a prompt cleavage of most of the native C3 in spite of 90% free alpha 1-antitrypsin. The consumption of alpha 2-macroglobulin, and especially of alpha 1-antitrypsin, decreased with increasing concentrations of aprotinin. Aprotinin was needed in a concentration of 60 microM to block trypsin-induced C3 cleavage almost completely. This concentration is about 20 times higher than ever used clinically. One possible explanation of the poor clinical effect of aprotinin to date in human pancreatitis is the need for this high concentration.
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PMID:An in vitro study of the influence of plasma protease inhibitors and aprotinin on trypsin-induced C3 cleavage in human serum. 618 50

The demembranation and reactivation of ejaculated rabbit spermatozoa have been studied. ATP, Mg, glutamate, dithiothreitol (DTT), and Tris-HCl were found to be essential for a good reactivation. With this experimental model, we investigated the effects of protease inhibitors on the reinitiation of movement by ATP and on the movement of already motile spermatozoa. Soybean trypsin inhibitor (STI) prolonged the length of reactivation by 7- to 8-fold, whereas pepstatin, antithrombin III, phenylmethylsulfonyl fluoride (PMSF), and alpha-1-antitrypsin had no significant effect. Aprotinin (1.5 micrograms/ml) and leupeptin (50 micrograms/ml) completely prevented the reinitiation of movement by ATP; aprotinin at the same concentration even blocked the movement of motile spermatozoa. A tissue-specific seminal plasma factor could also prevent both the reinitiation of movement and the movement of motile spermatozoa. However, it took 2-3 times the amount of seminal plasma to stop the movement than to prevent the reinitiation of movement. The inhibitor in the seminal plasma is most probably not a protease or an aprotinin-like protease inhibitor since a partially purified preparation of the seminal plasma inhibitor does not hydrolyze a trypsin substrate, is not inhibited by protease inhibitors and has no significant capacity to inhibit trypsin. The data suggest that aprotinin and the seminal plasma inhibitor block movement through different mechanisms. Aprotinin and the seminal plasma inhibitor represent two new tools to study the regulation of sperm movement.
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PMID:Aprotinin and a seminal plasma factor inhibit the motility of demembranated reactivated rabbit spermatozoa. 619 May 16

Inhibition of intraduodenal trypsin stimulates pancreatic secretion in rats and swine. This finding is controversial in healthy humans. The present study was designed to find whether a 'negative-feedback' mechanism exists in man. A 7-lumen tube equipped with two balloons was passed into the duodenum in 18 healthy volunteers. During a constant intravenous infusion of secretin (0.1 CU/kg/h) the duodenum was perfused with 0.9% NaCl solution (20 ml/10 min). Polyethylene glycol (10 g/l) served as nonabsorbable marker. Aprotinin (0.5 X 10(6) KIU/10 min or 1 X 10(6) KIU/10 min) was perfused intraduodenally during periods of constant pancreatic enzyme secretion for 30 min. During perfusion of the trypsin inhibitor aprotinin an almost complete inhibition of trypsin could be observed. However, at the same time or following the perfusion of aprotinin a significant augmentation of amylase, lipase or volume secretion did not occur. Thus, in the present study a negative-feedback control of pancreatic exocrine secretion by the intraduodenal trypsin concentration in man could not be demonstrated.
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PMID:Inhibition of intraduodenal trypsin does not stimulate exocrine pancreatic secretion in man. 619 29

Dietary fiber inhibits pancreatic enzyme activity--i.e., trypsin, lipase and amylase--in buffer solutions and in human duodenal juice in vitro. It is well established that oral administration of trypsin inhibitor stimulates the secretion and growth of the rat pancreas. In the present study, trypsin inhibitor (Trasylol) as well as dietary fiber such as pectin of low (37%) methoxylic esterification and wheat bran were found to stimulate pancreatic enzyme secretion in acute experiments in conscious rats with bile-pancreatic fistulae. Feeding for 10 days with wheat bran resulted in increased pancreatic weight and in increased protein and trypsinogen content. Administration of pectin of high (73%) methylic esterification caused increased pancreatic protein content and that of low methylic esterification increased pancreatic trypsinogen activity/milligram tissue. The results suggest that pectin and wheat bran may interfere with the feedback regulation of pancreatic enzyme secretion exerted by intraluminal trypsin, and, like trypsin inhibitor, have a secretagogue and trophic effect on the pancreas.
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PMID:Influence of dietary fiber on exocrine pancreatic function in the rat. 619 35


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