Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A basic phospholipase A was isolated from Vipera russellii snake venom. It induced a biphasic effect on washed rabbit platelets suspended in Tyrode's solution. The first phase was a reversible aggregation which was dependent on stirring and extracellular calcium. The second phase was an inhibitory effect on platelet aggregation, occurring 5 min after the addition of the venom phospholipase A without stirring or after a recovery from the reversible aggregation. The aggregating phase could be inhibited by indomethacin, tetracaine, papaverine, creatine phosphate/creatine phosphokinase, mepacrine, verapamil, sodium nitroprusside, prostaglandin E1 or bovine serum albumin. The venom phospholipase A released free fatty acids from synthetic phosphatidylcholine and intact platelets. p-Bromophenacyl bromide-modified venom phospholipase A lost its phospholipase A enzymatic and platelet-aggregating activities, but protected platelets from the aggregation induced by the native enzyme. The second phase of the venom phospholipase A action showed a different degree of inhibition on platelet aggregation induced by some activators in following order: arachidonic acid greater than collagen greater than thrombin greater than ionophore A23187. The longer the incubation time or the higher the concentration of the venom phospholipase A, the more pronounced was the inhibitory effect. The venom phospholipase A did not affect the thrombin-induced release reaction which was caused by intracellular Ca2+ mobilization in the presence of EDTA, but inhibited collagen-induced release reaction which was caused by Ca2+ influx from extracellular medium. The inhibitory effect of the venom phospholipase A and also lysophosphatidylcholine or arachidonic acid could be antagonized or reversed by bovine serum albumin. It was concluded that the first stimulatory phase of the venom phospholipase A action might be due to arachidonate liberation from platelet membrane. The second phase of inhibition of platelet aggregation and the release of ATP might be due to the inhibitory action of the split products produced by this venom phospholipase A.
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PMID:Biphasic effect on platelet aggregation by phospholipase a purified from Vipera russellii snake venom. 642 17

The platelet aggregation inhibitor purified from Agkistrodon halys snake venom inhibited rabbit platelet aggregations induced by thrombin, sodium arachidonate, collagen or ionophore A-23187. The IC50 was about 11 micrograms/ml in platelet aggregation regardless of which aggregation inducer was used. beta-Mercaptoethanol abolished both the phospholipase A enzymatic and platelet aggregation inhibitory activities of this venom inhibitor. p-Bromophenacyl bromide-treated venom inhibitor lost almost completely its phosphilipase A enzymatic activity, but retained its platelet aggregation inhibitory effect. In the presence of EGTA, the venom inhibitor still showed the same inhibitory activity on thrombin-, sodium arachidonate-, collagen- or ionophore A23187-induced platelet aggregations triggered by successive addition of Ca2+. The activation of platelet phospholipase A and the serotonin release reaction triggered by Ca2+ influx were unaffected by this venom inhibitor. It also inhibited the clot retraction of platelet-rich plasma. It is concluded that the inhibitory effect of the venom inhibitor on platelet aggregation is independent of its phospholipase A enzymatic activity. Its mode of action is different from those of other known platelet inhibitory drugs. This venom inhibitor possibly acts on a common step subsequent to platelet shape change, leading to inhibition of platelet aggregation.
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PMID:Mechanism of action of the platelet aggregation inhibitor purified from Agkistrodon halys (mamushi) snake venom. 642 79

Effects of seven purified phospholipases A2 from the venoms of snakes (Naja naja atra, Trimeresurus mucrosquamatus and T. gramineus) and honey bee (Apis mellifera) on rabbit washed platelet suspension in the absence of bovine serum albumin have been studied. Only phospholipases A2 from N. n. atra, T. mucrosquamatus and A. mellifera venoms induced platelet aggregation with small amounts of 14C-serotonin release. They showed tachyphylaxis and also cross-tachyphylaxis in inducing platelet aggregation. The former two phospholipases A2 exhibited biphasic responses in which irreversible aggregations appeared at concentrations of 1-10 micrograms/ml. At higher concentrations, they elicited the reversible aggregation. Exogenous Ca2+ was essential to their activity. Indomethacin and EDTA completely abolished both phospholipase A2 induced platelet shape change and aggregation, while mepacrine, prostaglandin E1, verapamil and nitroprusside inhibited only the aggregation response. p-Bromophenacyl bromide-modified phospholipases A2, which almost completely lost enzymatic activity, failed to induce platelet aggregation. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol inhibited the phospholipase A2-induced platelet aggregation. These phospholipases A2 induced thromboxane B2 formation which was inhibited by EDTA and indomethacin, but not by prostaglandin E1. Pre-treatment of platelet suspension with phospholipase A2 from N. n. atra or A. mellifera venom (50 micrograms/ml) inhibited platelet aggregation induced by sodium arachidonate or collagen, but not that induced by thrombin or ionophore A-23187. Exogenous sodium arachidonate or lysophosphatidylcholine also showed unaltered inhibitory spectrum on platelet aggregation. It is concluded that phospholipases A2 induce platelet aggregation by virtue of their enzymatic activity, cleaving the membrane phospholipids resulting in arachidonic acid release and formation of thromboxane A2. On the other hand, the cleaved products, lysophosphatidylcholine, arachidonic acid or arachidonate metabolites (via lipoxygenase pathway) may be responsible for anti-platelet activity.
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PMID:Effect of the purified phospholipases A2 from snake and bee venoms on rabbit platelet function. 644 10

Screening of the biochemical-pharmacological properties of the crude venom from the snake Lachesis muta indicated the presence of phospholipase A2 (PLA2; 5260 U/mg protein), procoagulant (2630 U/mg protein), platelet aggregating (43 U/mg protein) and caseinolytic activities (6670 U/mg protein). These activities were separated by filtration of the crude venom on Sephacryl S-200. The material containing PLA2 activity was further fractioned by DEAE-cellulose ion exchange chromatography into four active fractions (F-I to F-IV, containing 1.7, 1.2, 0.3, and 0.05% of the crude venom protein, respectively) by stepwise elution with buffers of increasing ionic strength. All fractions presented a molecular weight of approximately 15,000 and isoelectric points in the range pH 4.6-6.0. In addition to their indirect hemolytic activity, the partially purified fractions inhibited platelet aggregation induced either by collagen or thrombin. p-Bromophenacyl bromide-treated fractions lost both phospholipase A2 activity and their inhibitory effect on collagen-induced platelet aggregation.
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PMID:Partial purification and some physicochemical properties of phospholipases A2 from the venom of the bushmaster snake (Lachesis muta). 825 34

p-Bromophenacyl bromide, a potent alkylating agent inhibitor of phospholipase A2 and adenylate cyclase, potentiates hydrogen peroxide production in human platelets activated with thrombin. The maximal cooperative effect, specific for thrombin as inducer and potentiated by exogenous calcium, was observed at 2 microM BPB. Since it was shown that BPB is also a strong inhibitor of platelet aggregation (IC 50 = 3 +/- 1 microM) it is likely to suppose that the abnormal accumulation of hydrogen peroxide can influence platelet function.
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PMID:p-Bromophenacyl bromide potentiates hydrogen peroxide formation in human platelets challenged by thrombin and inhibits aggregation. 849 15