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:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of neutrophil elastase on endothelial prostacyclin (PGI2) production, nucleotide release, and responsiveness to vasoactive agents were compared with the effects of cathepsin G (the other major neutral protease of neutrophils), pancreatic elastase, trypsin, chymotrypsin, and thrombin. PGI2 production by pig aortic endothelial cells cultured on microcarrier beads and perfused in columns was stimulated in a dose-dependent manner by trypsin, chymotrypsin, and cathepsin G (1-100 micrograms/ml for 3 min). Thrombin, while active at low concentrations (0.1-10 National Institutes of Health U/ml), induced smaller responses. Neutrophil and pancreatic elastase had little or no effect on PGI2 production. Dose-dependent, selective release of adenine nucleotides was induced by neutrophil elastase (3-30 micrograms/ml). The other proteases were much less active; for example, trypsin (100 micrograms/ml) induced a response only approximately 5% as great as did 30 micrograms/ml neutrophil elastase. After exposure to 30 micrograms/ml neutrophil elastase, cells did not exhibit the characteristic burst of PGI2 production in response to extracellular ATP; responsiveness gradually returned after 40-120 min. This effect was not seen with the other proteases. Elastase partly inhibited responses to bradykinin and had no effect on PGI2 production that was stimulated by ionophore A23187. There was no evidence of cytotoxicity, as measured by release of lactate dehydrogenase. Neutrophil degranulation can generate concentrations of elastase and cathepsin G comparable with those tested in the present study, and the effects of these enzymes on endothelial function lead us to suggest that they may play a role in vasoregulation and vascular pathology.
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PMID:Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents. 643 44

Bradykinin-like activity was purified from acetic acid extracts of saline-perfused rat brains by gel filtration chromatography and two reverse-phase HPLC systems capable of resolving bradykinin from lysyl-bradykinin and other bradykinin analogs and fragments. Addition of [3H]bradykinin to extracts permitted calculation of recoveries and monitoring of chromatographic fractions. Fractions were examined by radioimmunoassay using a potent and highly specific antiserum raised against bradykinin-human albumin conjugates in rabbits. Bradykinin receptor-active material was also measured by radioreceptor assay using guinea pig ileum, as well as by a bioassay with the estrous rat uterus. Active material chromatographed as authentic bradykinin in all systems. Levels of 0.6 pmol/g whole rat brain were detected, with eight times higher levels in the hypothalamus. Activity increased up to 10-fold following treatment with trypsin; treatment with alpha-chymotrypsin or angiotensin-converting enzyme substantially reduced activity. Similar levels and distribution of bradykinin-like activity were also detected in guinea pig brain extracts. These data substantiate the existence of authentic bradykinin in mammalian brain.
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PMID:Identification of bradykinin in mammalian brain. 647 Jul 7

Stimulation of normal rat splenic T cells with pertussigen (lymphocytosis-promoting factor, LPF, from Bordetella pertussis) resulted in the release of a soluble factor that enhanced the glycosylation of IgE-binding factors during their biosynthesis. The soluble factor was detected by the ability of a culture filtrate of LPF-stimulated spleen cells to switch a T cell hybridoma, 23A4, from the formation of unglycosylated IgE-binding factor to the formation of glycosylated IgE-binding factor. The glycosylation-enhancing factor (GEF) had affinity for D-galactose, and the binding of the factor to hybridoma cells via a cell surface galactose was essential for modulation of IgE-binding factors. The GEF was inactivated by irreversible inhibitors of serine proteases such as phenylmethylsulfonyl fluoride, diisopropylfluorophosphate, and p-nitrophenyl ethylpentylphosphonate but was not affected by nonphosphorylating analogues of the organophosphorus compounds. Benzamidine, a competitive and reversible inhibitor of trypsin, also inhibited the glycosylation of IgE-binding factors by GEF. The factor could be purified by absorption to p-aminobenzamidine agarose followed by elution with benzamidine. The capacity of GEF to enhance the glycosylation of IgE-binding factors was inhibited by synthetic substrates of trypsin but not by substrates of chymotrypsin, indicating that GEF is a trypsin-like enzyme. Indeed, trypsin, plasmin, and kallikrein enhanced the glycosylation of IgE-binding factors during their biosynthesis. An inhibitor of trypsin-like enzyme(s), N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK), inhibited trypsin and plasmin but not kallikrein, and TLCK failed to inhibit the GEF-mediated enhancement of glycosylation. It was also found that bradykinin, the biologically active product of cleavage of kininogen by kallikrein, enhanced the glycosylation of IgE-binding factors. The results indicate that GEF is a kallikrein-like enzyme.
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PMID:Modulation of the biologic activities of IgE-binding factor. IV. Identification of glycosylation-enhancing factor as a kallikrein-like enzyme. 655 15

Four uterine-contractile substances (a, b, c and d) and three uterine-contractile substances (a', c' and d') were obtained from the reaction mixture of rat plasma kininogen with the kinin-forming enzyme in rat stomach and the homogenate of the rat stomach with 0.2% acetic acid, respectively. By high performance liquid chromatography with a Zorbax ODS reversed-phase column, the retention times of materials a, c and d were found to be equal to those of materials a', c' and d', and they were not equal to those of kallidin, methionyl-lysyl-bradykinin (MLBK) and bradykinin (BK). The retention time of material b was equal to that of BK. The uterine-contractile activities of the materials a, b, c, d, a', c' and d' were all abolished by chymotrypsin, but not by trypsin treatment. These materials all relaxed the isolated rat duodenum in the presence of atropine, dibenamine, diphenhydramine and propranolol, and they produced a fall in rabbit blood pressure after administration of atropine, dibenamine and propranolol. The content ratios of a: b: c: d and a': c': d' were 4: 4: 67: 25 and 65: 19: 16, respectively, as calculated from the uterine-contractile activities of these materials.
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PMID:Comparison of kinins derived from rat stomach tissue and produced by catheptic enzyme in rat stomach. 656 85

The kinin-forming enzyme of rat brain was studied by bioassaying kinin using a rat uterus. The enzyme released a kinin from the partially purified kininogen of rat plasma. The activity is exclusively distributed in the mitochondrial fraction and was detected in the pH range of 2.5-4.0 (optimally at pH 3.0). The enzyme was potently inhibited by pepstatin, but not by aprotinin. Released kinin was extracted by n-butanol and it was purified using Amberlite CG-50 absorption and CM-cellulose column chromatography. The elution profile of kinin from the CM-cellulose column did not coincide with that of bradykinin, Lys-bradykinin or Met-Lys-bradykinin. Isolated kinin was inactivated by treatment with chymotrypsin, but not with trypsin. In addition to the contractile activity on rat uterus, the kinin caused contraction of guinea pig ileum, with the response being potentiated by the presence of bradykinin-potentiator B. It also relaxed a rat duodenum, decreased rat blood pressure, and increased the vascular permeability in guinea pigs. Relative potencies of kinin on these pharmacological activities did not coincide with those of bradykinin. From these results, it is concluded that a kinin-forming enzyme is present in the rat brain. It is a cathepsin D-like enzyme, and furthermore, the enzyme releases a kinin-like peptide from the plasma kininogen fraction.
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PMID:Kinin-forming enzyme in rat brain mitochondria fraction and biological activity of a kinin released from rat plasma kininogen by this enzyme. 674 70

Activation of bovine plasma prekallikrein was investigated with several proteinases. Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC 3.4.21.8] by bovine activated Hageman factor, trypsin [EC 3.4.21.4] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC 3.4.22.2] and ficin [EC 3.4.22.3]. Activation of prekallikrein was also observed with bovine plasmin [EC 3.4.21.7], but not with bovine clotting factors Xa (Stuart factor) [EC 3.4.21.6] and IXa (Christmas factor) or thrombin [EC 3.4.21.5]. Urokinase [EC 3.4.99.26], Reptilase, collagenase [EC 3.4.24.3], elastase [EC 3.4.21.11], alpha-chymotrypsin [EC 3.4.21.1], Nagarse [EC 3.4.21.14], and stem bromelain [EC 3.4.22 4] did not convert prekallikrein to kallikrein. Plasma kallikrein activated to Hageman factor released kinin rapidly from bovine high molecular weight (HMW) kininogen. However, from bovine low molecular weight (LMW) kininogen, liberation of kinin was extremely slow. The kallikrein activity was inhibited by soybean trypsin inhibitor (SBTI), Trasylol, diisopropylfluorophosphate (DFP), and N-alpha-tosyl-L-lysine chloromethylketone (TLCK), but not by egg-white trypsin inhibitor (EWTI), lima bean trypsin inhibitor (LBTI), heparin or hexadimethrine bromide (Polybrene). The kallikrein formed an enzyme-inhibitor complex with SBTI and Trasylol, but not with LBTI. Prekallikrein did not react with SBTI. Prekallikrein consists of a single polypeptide chain of molecular weight about 90,000, as estimated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Activation of prekallikrein by Hageman factor was found to involve cleavage of the single peptide bond on the disulfide-bridged polypeptide chain, and no change of molecular weight was observed during the activation. The peptide bond cleaved in prekallikrein by the activation was an Arg-X peptide bond on a disulfide-bridged polypeptide chain.
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PMID:Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor. 676 24

Exposure of human blood polymorphonuclear leukocytes (PMN) to purified active plasma kallikrein resulted in PMN aggregation when kallikrein was present at concentrations ranging from 0.4 to 0.6 U/ml (0.18-0.27 microM). Kallikrein-induced PMN aggregation was not mediated through C5-derived peptides, because identical responses were observed whether or not kallikrein had been preincubated with an antibody to C5. Moreover, kallikrein was specific for aggregating PMN, because no aggregation was observed with Factor XII active fragments (23 nM), Factor XIa (0.6 U/ml or 15nM), thrombin (1.6 microM), plasmin (2 microM), porcine pancreatic elastase (2 microM), bovine pancreatic chymotrypsin (2 microM), or bradykinin (1 microM). Bovine pancreatic trypsin (2 microM) aggregated PMN, but to a lesser extent than kallikrein (0.18 microM). Kallikrein was a potent aggregant agent for PMN because similar responses were observed with kallikrein (0.5 U/ml or 0.23 microM) and an optimal dose (0.2 microM) of N-formyl-methionyl-leucyl-phenylalanine. In addition, PMN incubation with kallikrein resulted in stimulation of their oxidative metabolism as assessed by an increased oxygen uptake. Neutropenia and leukostasis observed in diseases associated with activation of the contact phase system may be the result of PMN aggregation by plasma kallikrein.
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PMID:Purified human plasma kallikrein aggregates human blood neutrophils. 691 55

Four uterine-contractile substances (a, b, c and d) were extracted from procedures with acetic acid, n-butanol, distilled water, and methanol from the reaction mixture obtained by incubating rat plasma kininogen with the kininforming enzyme in the rat stomach. Gradient and equilibrium chromatography on SP-Sephadex C-25 columns were carried out with the extract containing these materials (a, b, c and d). The materials could not be separated by chromatography on SP-Sephadex C-25, but were separated by high performance liquid chromatography (HPLC) with a Zorbax ODS reversed-phase column. All the materials (a, b, c and d) contracted the rat uterus and relaxed the rat duodenum. The uterine-contractile activity of the materials was abolished by chymotrypsin, but not by trypsin treatment. The retention times of materials a, c and d on HPLC were different from that of kallidin, MLBK, bradykinin (BK) and neurotensin; but the retention time of material b was equal to that of BK. The content ratio of a: b: c: d was 4: 4: 67: 25, calculated from the uterine-contractile activity of these materials. The apparent molecular weight of the major material c, estimated by gel chromatography, was 1650. Material c contracted the rat uterus (1.2 x 10(-10) g/ml), relaxed the rat duodenum (2 x 10(-10) g/ml), and produced a fall in rabbit blood pressure (4.4 x 10(-8) g/kg). Material c was classified as a biologically BK-like peptide which is distinct from kallidin, MLBK, BK and neurotensin.
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PMID:Kinin formation by catheptic enzyme in rat stomach. 716 63

A bradykinin (BK)-like substance (P1) in the rat stomach was extracted with acetic acid, n-butanol, distilled water and methanol. The gradient and equilibrium chromatography were carried out on SP-Sephadex C-25 columns with the extract containing P1. P1 had a different retention time from BK, kallidin and methionyl-lysyl-bradykinin (MLBK), on the equilibrium chromatography. The apparent molecular weight of P1 estimated by gel chromatography was over 1,300. P1 was classified as a biologically BK-like peptide of mammalian origin which is distinct from BK, kallidin and MLBK. Another kind of biologically active substance (P2) which contracts the isolated rat uterus and duodenum was detected during the course of the extraction and purification of P1. The contractile activity of P2 was abolished by the presence of dibenamine or methysergide, but was not influenced by chymotrypsin, trypsin or papain digestion. The hypotensive effect of P2 on rabbit blood pressure was similar to that of serotonin (5-HT). The retention times of P2 on the equilibrium chromatography on the SP-Sephadex C-25 column, and on the gel chromatography were the same as those of 5-HT. P2 proved to be 5-HT.
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PMID:A bradykinin-like substance in rat stomach. 720 76

Potentiation of the activity of bradykinin on the isolated guinea pig ileum was studied using a designed test system with the synthetic peptides Leu-Val-Glu-Ser-Ser-Lys, Thr-Pro-Val-Ser-Glu-Lys, derivatives of the former coupled to the N- and C-terminals of bradykinin and two peptides with phenylalanine substituted with its isomer L-3-amino-3-phenylpropanoic acid in the 5- and 5,8-positions in bradykinin respectively. On average, two times potentiation effects were obtained at 10-6 to 10-8 M concentrations of the peptides. After elimination of the basic lysine no potentiation occurred with synthetic Leu-Val-Glu-Ser-Ser. With the [beta Phe5,8]-bradykinin a mixed sensitizing/potentiating effect was observed, suggesting that a separation of the two effects may be difficult with an intact receptor structure of this kind. This peptide was not hydrolyzed by carboxypeptidase B or chymotrypsin.
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PMID:Potentiation of bradykinin with synthetic peptides on guinea pig ileum. 730 68


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