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)

When the effect of MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4 H-pyrano [3,2-c] quinoline-2-carboxylic acid) on histamine release from rat peritoneal mast cells induced by compound 48/80 was studied, MY-1250 caused a significant inhibition of histamine release at concentrations higher than 3 microM. Furthermore, the compound inhibited not only 45C a uptake into the mast cells but also Ca2+ release from the intracellular Ca store at a concentration of 10 microM in both cases. By contrast, MY-1250 did not affect either histamine release from permeabilized mast cells induced by TPA, IP3 and GTP gamma S or Ca2+ release from the endoplasmic reticulum induced by IP3. In the chopped lung preparations, MY-1250 at doses of 10 and 100 microM caused a significant inhibition in histamine release from the pieces of actively sensitized guinea pigs exposed to antigen and simultaneously prevented a decrease in intracellular cAMP contents taking place in association with antigen-antibody reaction. No significant changes were effected by MY-1250 in alpha-chymotrypsin activity and phospholipase A2 activity. Also, no antagonistic effects on LTD4 and PAF were observed.
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PMID:Inhibitory effect of MY-1250 on histamine release from rat peritoneal mast cells and guinea pig lung fragments: the elucidation of the mechanism. 171 61

Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. In this paper we show that ajoene has a unique locus of action, that is not shared by any other known antiplatelet compound. For example, ajoene inhibits agonist-induced exposure of fibrinogen receptors, as well as intracellular responses such as activation of protein kinase C and the increase in cytoplasmic free calcium induced by receptor-dependent agonists (collagen, ADP, PAF, low-dose thrombin). On the other hand, with agonists that can by-pass (at least partially) the receptor-transductor-effector sequence, such as high-dose thrombin, PMA, NaF, only the exposure of fibrinogen receptors is blocked by ajoene. Binding of fibrinogen to chymotrypsin-treated platelets is only slightly inhibited by ajoene. The results reported here also show that: (a) ajoene does not act as a calcium chelator, does not impair the initial agonist-receptor interaction and does not influence the basal levels of intracellular inhibitors of platelet activation such as cyclic GMP; (b) the locus of action of ajoene is a yet unknown molecular step that links, in the case of physiological agonists, specific agonist-receptor complexes to the sequence of the signal transduction system on the plasma membrane of platelets. In the case of non-physiological, receptor-independent agonists (PMA, NaF), we can only speculate on the hypothesis that they somehow mimic the effect of the agonist-receptor complexes on the signal transduction system; and (c) the exposure of fibrinogen receptors is not a direct consequence of other intracellular processes. These observations clearly show, for the first time, that the exposure of fibrinogen receptors is a membrane event proximally and obligatorily coupled to the occupancy of other membrane receptors by their agonists without any intervention by the cytoplasmic biochemical processes. Additional results support the involvement of G-proteins in these early events of platelet activation. Furthermore, a role of the beta tau subunits of G-proteins in the exposure of fibrinogen receptors is proposed.
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PMID:Evidence for direct coupling of primary agonist-receptor interaction to the exposure of functional IIb-IIIa complexes in human blood platelets. Results from studies with the antiplatelet compound ajoene. 191 78

Butylidenephthalide inhibited, in a dose-dependent manner, the aggregation and release reaction of washed rabbit platelets induced by collagen and arachidonic acid. Butylidenephthalide also inhibited slightly the platelet aggregation induced by PAF and ADP, but not that by thrombin or ionophore A23187. Thromboxane B2 formation caused by collagen, arachidonic acid, thrombin and ionophore A23187 was in each case markedly inhibited by butylidenephthalide. Butylidenephthalide inhibited the aggregation of ADP-refractory platelets, thrombin-degranulated platelets, chymotrypsin-treated platelets and platelets in the presence of creatine phosphate/creatine phosphokinase. Its inhibition of collagen-induced aggregation was more marked at lower Ca2+ concentrations in the medium. The aggregability of platelets inhibited by butylidenephthalide could be recovered after the washing of platelets. In human platelet-rich plasma, butylidenephthalide and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine. Prostaglandin E2 formed by the incubation of guinea-pig lung homogenate with arachidonic acid could be inhibited by butylidenephthalide, indomethacin and aspirin. It is concluded that the antiplatelet effect of butylidenephthalide is mainly due to an inhibitory effect on cyclo-oxygenase and may be due partly to interference with calcium mobilization.
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PMID:Antiplatelet effect of butylidenephthalide. 310 95

A monoclonal antibody, SZ-2, reacts specifically on human platelets and megakaryocytes. The platelets from 10 normal donors are bound to 15,200 +/- 4,100 SZ-2 molecules/platelet. The antigen recognized by SZ-2 is chymotrypsin-sensitive but neuraminidase-insensitive, and has been identified as glycoprotein Ib (GPIb) by an affinity chromatography technique. SZ-2 is different from other monoclonal antibodies to GPIb. It inhibits not only platelet aggregation induced by ristocetin, but also platelet aggregation induced by collagen (type I) and by PAF. SZ-2 also inhibits platelet serotonin and beta-thromboglobulin release in response to these stimuli.
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PMID:Studies on monoclonal antibodies against human platelets--a monoclonal antibody to human platelet glycoprotein I--SZ-2. 365 97

The amino sugars glucosamine, galactosamine and mannosamine (30 mM) inhibited aggregation of human or rabbit platelets induced by ADP, collagen, thrombin, PAF or high concentrations of sodium arachidonate. 125I-fibrinogen binding during ADP-induced aggregation, and release of amine storage granule contents were also inhibited. Increasing the calcium concentration of the suspending medium to 5 mM did not overcome the inhibitory effect on the release reaction. The amino sugars deaggregated rabbit platelets that had been aggregated by ADP, collagen or thrombin, but deaggregated human platelets readily only when ADP was used as the aggregating agent. Fibrinogen-induced aggregation of chymotrypsin-treated platelets was blocked by the amino sugars. They did not inhibit platelet adherence to a collagen-coated glass surface, nor affect release of granule contents from the adherent platelets. Aggregation and release induced by low concentrations of sodium arachidonate or the divalent cation ionophore A23187 were potentiated, indicating that the effects of the amino sugars on platelets are more complex than simple inhibition of the lectin-like activity that becomes available on the surface of platelets that have undergone the release reaction. One of the effects of the amino sugars, however, is interference with the binding of fibrinogen to platelets. The effects of the amino sugars are shared by other primary amines.
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PMID:Effect of amino sugars on platelet aggregation and on fibrinogen binding. 649 68

FWPs are usually stable for several months. However, in less than a week, one lot of FWPs lost its ability to aggregate with bovine PAF or human vWF plus ristocetin. Initial experiments suggested that the loss of aggregability was caused by contamination of the FWPs with an extracellular protease of Serratia marcescens. Highly purified protease preparations from the culture filtrates of S. marcescens (SP), as well as from two strains of Pseudomonas aeruginosa, destroyed the aggregability of FWPs as a function of time and concentration. On the basis of azocasein units, the SP was found to be at least eight times more potent against FWPs as a substrate than either of the P. aeruginosa proteases. The effect of SP on FWP aggregability was inhibited by prior EDTA treatment and was restored by addition of Zn2+ in slight molar excess. Purified PAF, but not dilutions of bovine plasma, lost all PAF activity when incubated with SP. SP-treated FWPs would still aggregate with 10 microgram/ml polylysine. SP digestion of FWPs was more selective than digestion with trypsin or chymotrypsin, on the basis of both the polyacrylamide gel electrophoresis pattern and the amount of protein in the platelet digest supernatant. SP does not aggregate fresh washed platelets or initiate the release reaction but renders them unaggregable with vWF. SP and related proteases may be useful in the study of platelet membranes.
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PMID:The effect of extracellular proteases from gran-negative bacteria on the interaction of von Willebrand factor with human platelets. 678 Jun 41

Lebetins 1 and Lebetins 2, two polypeptide groups that inhibit platelet aggregation, were isolated from Vipera lebetina venom by gel filtration and reverse phase chromatography. Amino acid sequencing indicated that the first group contains two major polypeptides of 13 and 12 residues; their molecular weight was determined by electrospray mass spectrometry. The second was composed of two peptides of 38 and 37 residues, each with one disulfide bond. Sequence analysis revealed neither RGD sequence nor homology with other proteins including known snake or tick polypeptides. Lebetins 1 were Pro and Lys rich peptides and their sequences were identical to the N-terminus of Lebetins 2. Lebetins inhibited platelet aggregation induced by thrombin, collagen and PAF-acether. The 50% concentration that inhibited human and rabbit platelet aggregation induced by thrombin was 590 nM and 125 nM for Lebetins 1 and 100 nM and 8 nM for Lebetins 2, respectively. Lebetins 1 and Lebetins 2 also inhibited fibrinogen-induced aggregation of alpha-chymotrypsin-treated platelets as well as in vivo collagen-induced thrombocytopenia in rats with half effective doses of 2 nmol/kg and 4.2 nmol/kg, respectively. Lebetins were not toxic after intravenous injection into mice and rats. These polypeptides form novel platelet inhibitors that could be used to delineate further the mechanisms of platelet aggregation and serve as a model for developing antithrombotic agents.
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PMID:Novel anti-platelet aggregation polypeptides from Vipera lebetina venom: isolation and characterization. 876 4

Cerastatin, a potent platelet aggregation inhibitor, was purified by gel filtration on Sephadex G-75, followed by two ion exchange chromatographies on Mono-S columns. Cerastatin is a neutral glycoprotein (pI = 6.2) of 32 kDa, made up of at least three subunits. It is devoid of phospholipase A2, esterase, fibrinogenolytic and amidolytic activities. It inhibits aggregation of washed platelets, induced by either collagen, PAF acether or thrombin, with similar IC50 of 2.3 nM. Cerastatin also inhibits the thrombin-induced clot retraction of platelet-rich plasma. It does not inhibit the amidolytic or the procoagulant activities of thrombin Cerastatin caused no lytic effect on platelet membranes since it did not cause release of lactate dehydrogenase. Pretreatment of platelets with cerastatin irreversibly inhibits the aggregation induced by thrombin. Also cerastatin completely inhibits the fibrinogen-induced aggregation of alpha chymotrypsin-treated platelets. Cerastatin therefore inhibits platelet aggregation by interfering with the interaction of fibrinogen with fibrinogen receptors.
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PMID:Cerastatin, a new potent inhibitor of platelet aggregation from the venom of the Tunisian viper, Cerastes cerastes. 902 15

Proteinaceous inhibitors with high inhibitory activities against human neutrophil elastase (HNE) were found in seeds of the Tamarind tree (Tamarindus indica). A serine proteinase inhibitor denoted PG50 was purified using ammonium sulphate and acetone precipitation followed by Sephacryl S-300 and Sephadex G-50 gel filtration chromatographies. Inhibitor PG50 showed a Mr of 14.9 K on Sephadex G-50 calibrated column and a Mr of 11.6 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PG50 had selective activity while cysteine proteinases (papain and bromelain) and serine proteinases (porcine pancreatic elastase and bovine chymotrypsin) were not inhibited, it was strongly effective against serine proteinases such as bovine trypsin and isolated human neutrophil elastase. The IC50 value was determined to be 55.96 microg.mL-1. PG50 showed neither cytotoxic nor haemolytic activity on human blood cells. After pre-incubation of PG50 with cytochalasin B, the exocytosis of elastase was initiated using PAF and fMLP. PG50 exhibited different inhibition on elastase release by PAF, at 44.6% and on release by fMLP, at 28.4%. These results showed that PG50 preferentially affected elastase release by PAF stimuli and this may indicate selective inhibition on PAF receptors.
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PMID:A serine proteinase inhibitor isolated from Tamarindus indica seeds and its effects on the release of human neutrophil elastase. 1582 May