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 synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9% NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl. Studies with Russell's viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation.
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PMID:Studies on the action mechanism of the antihemostatic effect of lodopeptides. 0 4

We have tested a platelet aggregation inhibitor in the incubation fluid of deendothelialized fragments of the rat aorta and compared it with that of "intact" fragments. Some of the properties of the aortic inhibitor, and its effects on platelet adhesion to collagen fibrils, on platelet factor-3 (PF-3) availability, and on the activated partial thromboplastin time (APTT) and thrombin time (TT) were also evaluated in comparison with similar effects exerted by PGI2. We found that the incubation fluid of deendothelialized aortic samples contained inhibitor activity comparable with that of "intact" samples. The aortic inhibitor had similar properties to PGI2. The aortic inhibitor and PGI2 slightly inhibited light transmission changes of EDTA-PRP following exposure to collagen. However, scanning electron microscopy showed no appreciable difference in platelet adhesion to collagen fibrils. PGI2 and the aortic inhibitor inhibited Kaolin-induced PF-3 availability, but did not prolong the APTT or TT.
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PMID:Generation of a PGI2-like activity by deendothelialized rat aorta. 38 19

The individual and combined effects of PGD2, PGI2 and an aortic proteoglycan on human platelet aggregation and plasma clotting were studied. PGI2 was at least 10 times more potent than PGD2 in inhibiting platelet aggregation. Small doses of prostaglandins inhibited ADP- and thrombin-induced aggregation, but only prolonged aggregation time without affecting the extent of arachidonic acid (AA)-induced aggregation. Small doses of prostaglandins did not affect thrombin-induced clotting of PRP. Large doses of prostaglandins abolished platelet aggregation and prolonged the onset of thrombin-induced clotting. The aortic proteoglycan (APG) had no appreciable effect on ADP- or AA-induced aggregation. Small doses of APG abolished thrombin-induced clotting, while large doses of APG suppressed both clotting and aggregation induced by thrombin. PGI2 and PGD2 showed additive inhibition of platelet aggregation regardless how the aggregation was induced. APG and prostaglandins showed additive inhibition of only thrombin-induced aggregation. APG, but not any of the prostaglandins, prolonged clotting time of PPP. This prolongation was not potentiated by PGI2 or PGD2.
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PMID:Combined effect of prostaglandins and an aortic proteoglycan on platelet aggregation and plasma clotting. 39 32

A comparison has been made of some effects of a semi-synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti-factor Xa activity was obtained, in the agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti-Factor Xa acitvity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.
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PMID:Comparison of heparin and a semi-synthetic heparin analogue, A73025. II. Some effects on platelet function. 60 58

Geometries of platelets in citrated PRP obtained from normal donors (17) and donors (5) with a hereditary dominant giant platelet syndrome, herein referred to as "Montreal platelet syndrome" (MPS), are compared. The measured geometric axial ratio (rp = thickness/diameter) is used to classify platelet morphologies into three groups: discocytes (rp less than 0.5), disco-echinocytes (rp = 0.5 to 0.9), sphero-echinocytes (rp greater than 0.9). MPS discocytes are normal sized; however, MPS sphero-echinocytes and disco-echinocytes have mean volumes approximately two times larger than normal. It is demonstrated that these larger-than-normal sized MPS platelets can be produced directly from MPS discocytes by treatment with agents known to induce platelet shape change (adenosine diphosphate, thrombin, and incubation at 4 degrees C). Treatment of platelets obtained from normal donors which have been resuspended in MPS PPP and ADP or incubation at 4 degrees C causes the formation of normal-sized disco-echinocytes and sphero-echinocytes. The diameters of MPS disco-echinocytes are identical to the diameters of MPS platelets observed on peripheral blood smear, whereas those of MPS sphero-echinocytes are approximately 20% lower. It is suggested that the appearance of abnormally large platelets in MPS is related to a defect in the mechanism which regulates platelet size and shape during shape change.
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PMID:Shape-changing agents produce abnormally large platelets in a hereditary "giant platelets syndrome (MPS)". 75 24

When gel filtration is used to transfer platelets from plasma into an established environment, alterations in platelet characteristics may result from the change in environment or from the effects of platelet contact with the gel matrix. To approach the problem of evaluating the relative contributions from these sources, a Sepharose 2B matrix was employed and platelets transferred from citrate anticoagulated PRP into autologous PPP to yield plasma-GFP. Platelet recoveries averaged 93%. PRP: plasma-GFP pairs were found to be indistinguishable with respect to: morphology; ADP, thrombin or collagen-induced aggregation response; uptake of 5-hydroxytryptamine (5-HT) or adenosine; and thrombin or collagen-induced release of accumulated 5-HT or adenosine. Pairs are distinguishable by prostaglandin E2 synthesis assayed immediately after filtration.
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PMID:Effects of matrix contact during gel filtration of human platelets in plasma. 103 35

In the PRP of anaphylactic rats, ADP, collagen and thrombin induced platelet aggregation was considerably reduced. Reduced aggregability could be transferred to normal platelets by suspending them in the PPP of anaphylactic animals and the impaired aggregation of platelets from animals undergoing anaphylaxis could be restored by exchanging their plasma for that of normal controls. Ellagic acid, a known activator of factor XII, produced similar alterations as obtained in anaphylactic shcok. It is suggested that the inhibition of platelet aggregation is due to the anaphylactic activation of factor XII and this mechanism may be of importance in rat anaphylaxis.
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PMID:Reduced aggregability of platelets in rat anaphylaxis. 126 97

Rhynchophylline (Rhy) inhibited rabbit platelet aggregation induced by arachidonic acid (AA), collagen, and ADP. The values of IC50 were 0.72, 0.74, and 0.67 mmol.L-1, respectively. Rhy reduced the thromboxane B2 (TXB2) generation in PRP induced by collagen but failed to reduce that induced by AA. Rhy suppressed malondialdehyde (MDA) formation in platelet suspension stimulated by thrombin, inhibited the platelet factor 4 (PF4) release. It did not alter intraplatelet cAMP concentration. Rhy 10-20 mg.kg-1 iv showed a significant inhibition of venous thrombosis and cerebral thrombosis in rats.
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PMID:Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis. 131 85

A new method has been developed to investigate the direct effect of endothelial cells on platelet aggregation in the presence of cultured confluent human EC monolayers. The inside of the disk shaped cuvettes are covered by human umbilical vein ECs. The cuvettes rotate in the light beam of a photometer. In these cuvettes the effect of different aggregation inducers was inhibited in a concentration-dependent manner, e. g. for collagen at 0.5 microgram/ml, ADP at 5 x 10(-7) M, epinephrine at 5 x 10(-7) M and thrombin at 0.05 U/ml final concentration. (Platelet count 5 x 10(5)/microliters). Higher concentrations of the inducers led to irreversible platelet aggregation and were used for testing of antiplatelet drugs. In this system we detected a synergism between the antiaggregatory effect of the EC monolayer and that of SIN 1 (Cassella, Frankfurt/Main) the main metabolite of Molsidomine. 10 micrograms/ml PRP of SIN 1 alone partially inhibited platelet aggregation induced by 1 microgram/ml collagen and 10(-6) M ADP respectively in uncovered aggregation cuvettes. In the presence of an EC monolayer complete inhibition of platelet aggregation was obtained at a 5-fold final concentration of both inducers. After pretreatment of ECs with 1 mmol ASA over 30 min. the antiaggregatory effect of SIN 1 decreased, but was more pronounced (50%) than in uncovered cuvettes (25%).
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PMID:[Effect of SIN 1 on the interactions of endothelial cells and thrombocytes]. 177 29

The present in vitro study of the effects of iron on the blood coagulation mechanism in rats showed that addition of ferrous sulphate to pooled rat plasma resulted in inhibition of blood coagulation, as shown by prolongation of the clotting parameters tested, an effect which was dose-dependent. In vitro addition of ferrous sulphate to rat PRP in doses of 2-5 mg/ml significantly decreased platelet aggregation in response to ADP, while collagen-induced aggregation was significantly diminished in presence of the higher doses of ferrous sulphate (4-5 mg/ml). Also, preincubation of ferrous sulphate with thrombin or with pure fibrinogen indicated that iron could produce decrease of thrombin activity as well as impairment of fibrinogen clottability. In vitro addition of copper sulphate (300-1000 micrograms/ml) elicited an anticoagulant effect, though thrombin time was markedly shortened with all tested concentrations of copper sulphate. Addition of copper sulphate to PRP produced inhibition of platelet aggregation in response to PRP produced inhibition of platelet aggregation in response to ADP and to collagen. Preincubation of copper sulphate with thrombin resulted in slight enhancement of thrombin activity followed by inhibition, while preincubation of copper sulphate with pure fibrinogen caused only minimal impairment of fibrinogen clottability. Also, addition of gold chloride in doses of 50-500 micrograms/ml to plasma in vitro produced a dose-dependent progressive prolongation of all clotting parameters tested, the effects reaching a maximum after 30 min. incubation. Further the in vitro addition of gold chloride to rat PRP resulted in marked inhibition of platelet aggregation in response to both ADP and collagen. In addition, preincubation of gold chloride with thrombin or with pure fibrinogen showed that gold exerted an antithrombin action and prolonged the fibrinogen clotting time indicating impaired fibrinogen clottability.
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PMID:In vitro effects of trace elements on blood clotting and platelet function. A--Iron, copper, and gold. 180 Jun 20


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