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)

Aggregation induced in human platelets by thrombin (TH), collagen (COLL) or the Ca++ ionophore, A23187, was blocked by dibucaine and tetracaine. COLL-induced aggregation was blocked at lower concentrations of anesthetics (0.01-0.5 mM) than TH- or A23187-induced aggregation (0.2-2.0 mM). The rate and magnitude of the release of adenosine diphosphate, Ca++ and serotonin was also decreased by anesthetics. Secretion due to COLL, but not to TH, required extracellular Ca++ and was accompanied by increased uptake of 45Ca which was inhibited by local anesthetics. A23187-induced secretion was partially dependent upon external Ca++ and was accompanied by increased 45Ca uptake. Anesthetics increased 45Ca uptake when added before, but not after, A23187. This effect can be explained by postulating that the anesthetics prevent the release of an internal pool of Ca++, thereby affecting the Ca++ gradient between platelet cytoplasm and extracellular fluid. Platelets degramulated, but not aggregated, by exposure to TH in the presence of ethylene glycol bis(beta--aminoethyl ether)-N, N'-tetraacetic acid and plasmin were isolated by sepharose gel filtration. Such platelets did not aggregate with COLL or TH, but did aggregate with A23187-an effect blocked by local anesthetics. Thus platelet aggregation and secretion are independent Ca++-requiring processes, each of which is inhibitable by local anesthetics, presumable by blocking Ca++ influx or the mobilization of intracellular Ca++ stores.
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PMID:An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. 77 86

Thrombin-induced platelet aggregation has been generally believed to be irreversible. However, thrombin-induced aggregation of washed platelets is reversible if fibrin formation is prevented or the fibrin which binds the platelets together is removed from the platelet aggregates. After treatment with high concentrations of thrombin (0.5 units/ml) single platelets can be recovered that have lost practically all of their releasable serotonin and adenine nucleotides. These platelets are able to aggregate upon addition of low concentrations of ADP in the presence of fibrinogen. They aggregate in response to the ionophore A23, 187 in the absence of added fibrinogen, whereas sodium arachidonate-induced aggregation requires added fibrinogen. Thrombin-treated platelets change their shape in response to collagen in the absence of fibrinogen, and will aggregate upon the addition of collagen providing fibrinogen is present. This response to collagen can be blocked with aspirin but not with a mixture of creatine phosphate/creatine phosphokinase. Upon a second exposure to thrombin, thrombin-pretreated platelets do not change their shape and do not undergo aggregation. Thrombin-pretreated platelets will not retract a thrombin-induced fibrin clot unless ADP, sodium arachidonate, the ionophore A23, 187 or collagen are added together with thrombin. The ability of thrombin-treated platelets to adhere to the exposed subendothelial surface of the rabbit aorta is reduced, compared with untreated control platelets. The thrombin-treated platelets shorten the bleeding time of thrombocytopenic rabbits. However, the are not as effective in shortening the bleeding time as normal control platelets. When injected into rabbits with a normal platelet count, the thrombin-treated platelets that circulate after infusion survive for the same length of time as untreated control platelets. These findings indicate that thrombin-induced platelet aggregation with extensive release of granule constituents is not irreversible and that thrombin treatment does not cause irreversible damage of all platelets that would lead to their immediate elimination from the circulation. Furthermore, these platelets can still be haemostatically effective. It is conceivable that platelets that have lost their amine storage granule contents during a release reaction in vivo, such as may occur in certain cases of intravascular coagulation and repeated episodes of thrombosis, may be found in the circulation of man.
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PMID:In vitro and in vivo functions of thrombin-treated platelets. 78 86

The cationic protein isolated from the granules of neutrophilic polymorphonuclear leukocytes inhibited the aggregation of human platelets as induced by collagen, thrombin, ristocetin, aggregated IgG by approximately 50% and anti-C1q by 75% but had no effect on aggregation-induced by ADP.
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PMID:Inhibition of platelet aggregation by cationic protein from polymorphonuclear leukocytes. 79 7

Treatment of human platelets with purified bovine Factor VIII caused three types of aggregation: (a) primary agglutination; (b) secondary aggregation involving the platelet release reaction; and (c) super-aggregation, in which the platelets were gathered into only a few large clumps. Removal of calcium ions or treatment with p-hydroxymercuiriphenyl sulfonate blocked the release reaction, but not primary agglutination or super-aggregation. Platelets treated with formalin were not aggregated by ADP, thrombin, or collagen, but were agglutinated by bovine Factor VIII, although they did not show super-aggregation. For malin-treated platelets were agglutinated by phytohemagglutinin P less extensively and less rapidly than by bovine Factor VIII. Treatment of platelets and Factor VIII with neuraminidase released 60 and 53%, respectively, of the sialic acid residues without affecting the agglutination reaction or the procoagulant activity of the Factor VIII. Agglutination was inhibited by high salt concentrations, dextran sulfate, and heparin. During agglutination, both the procoagulant and platelet-agglutinating activities of Factor VIII became bound to the platelet surface.
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PMID:The interaction of bovine factor VIII with human platelets. 80

Release of 14C-serotonin from human platelets prelabeled with 14C-5-hydroxytryptamine was measured during platelet aggregation induced by Staphylococcus aureus. Platelet-bacteria interaction (PBI) was as potent a stimulus of the platelet release reaction as collagen, thrombin, or epinephrine. Inhibitors which blocked platelet aggregation also prevented the release reaction of PBI. Sequential measurements of release, when correlated with nephelometry of aggregation, showed close correlation between the onset of release and the onset of platelet shape change and early aggregation. Ultrastructural studies with polylysine, an agent capable of polymerizing platelet granule contents, revealed that granule components are secreted to the region of the bacteria trapped between platelets in the forming aggregates. Platelet peroxidase activity remained localized within the dense tubular system of the platelets.
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PMID:Platelet interaction with bacteria. IV. Stimulation of the release reaction. 81 Nov 23

Human platelet factor 4 antigen (PF4 antigen) was measured in platelets and in plasma by means of single radial immunodiffusion. Anti-PF4 antibody obtained in rabbits by injecting highly purified human PF4 was monospecific in double immunodiffusion and in quantitative "rocket" immunoelectrophoresis. A high degree of correlation was observed between the precipitation zones in the radial immunodiffusion method and the amount of purified PF4 (in the range of 0.6 to 50.0 mug per milliliter) or the number of platelets in plasma (in the range of 5 x 10(6) to 1.6 x 10(8) platelets per milliliter applied. The sensitivity of the method was 30 to 125 times higher as compared with clotting assay (antiheparin activity) and the standard error of the method was 2.3 per cent. The method was specific for the antigen present in platelets since human leukocytes and erythrocytes gave negative results. Release of PF4 antigen from washed platelets challenged with thrombin, collagen, ADP, and antigen-antibody complexes was measured by the radial immunodiffusion assay. It usually paralleled the release of 3H-serotonin but PF4 antigen was a more sensitive marker for platelet release reaction. Release of PF4 antigen was usually 2 to 4 times higher than release of the antiheparin activity as measured by clotting assay when both were compared as percentage of total content in platelets. The level of PF4 antigen was determined in platelet-rich plasma (PRP) and platelet-free plasma (PFP) obtained from 12 healthy volunteers. While the mean level of extraplatelet pool of PF4 antigen in PFP was 0.72 +/- 0.92 mug per milliliter, PRP contained 80 +/- 22 mug of PF4 antigen per 10(9) platelets. Addition of thrombin (1 U. per milliliter) liberated all of the PF4 antigen (78 +/- 24 mug) present in PRP but ADP (50 muM) released only 31 +/- 22 mug of PF4 antigen per 10(9) platelets. The presence of heparin did not interfere with the assay of intraplatelet or extraplatelet PF4 by single radial immunodiffusion. The method described represents a simple, sensitive, quantitative, and specific assay for human PF4 antigen possessing antiheparin activity.
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PMID:Immunoassay of human platelet factor 4(PF4, antiheparin factor) by radial immunodiffusion. 81 25

Human blood platelets in ACD plasma were stored in sterile plastic bags for 24-96 h at the ambient temperature without agitation. No spontaneous aggregation nor bacterial contamination were noted. A progressive loss of the following parameters was seen: platelet count; ADP-, thrombin-, collagen-, and epinephrine-induced platelet aggregation; platelet factor 3 activity; reversible response to the osmotic shock; volumetric constants; amount of UV-absorbant material; 14C-5-hydroxytryptamine and 3H-adenosine uptake and release; platelet population pattern and glycogen synthesis activity. The platelet aggregation and release, the osmotic shock test, and the platelet population pattern appear to better illustrate the early changes during platelet storage and to account for the 25-42% of recirculation of 24 h stored platelets administered into thrombocytopenic patients. As stated by Murphy and Gaardner, platelets stored at 20-22 degrees C with or without agitation, although having failed to retain total functional and biochemical capacities, paradoxically seem to recuperate in vivo as shown by survival data and hemostatic effects.
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PMID:Studies on human platelets stored at 20-22 degrees C without agitation. 82 71

In four patients, platelet aggregation with arachidonate was absent but was normal with "Labile Aggregation Stimulating Substance". ADP (10muM) aggregation was always reversible; collagen aggregation was absent and those induced by thrombin and ristocetin were normal. Collagen did not induce 14C-serotonin release but there was some release with thrombin. There was no thromboxan B2 synthesis in these platelets. Two patients showed hereditary hemostasis defect and the others acquired cyclo-oxygenase deficiency.
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PMID:[Thrombocytopathia with cyclo-oxygenase deficiency]. 82 36

The effects of lysolecithin (LPC) on aggregation, serotonin release, shape, and lysis of rabbit, pig, or human platelets in platelet-rich plasma (PRP) or Tyrode albumin solution were examined during prolonged incubation. LPC added to citrated or heparinized PRP from humans or rabbits at a final concentration above 100 muM caused instantaneous inhibition of platelet aggregation induced by adenosine diphosphate (ADP), epinephrine (human PRP only), collagen, or thrombin. The inhibitory effect of LPC was found to be partially reversible over a period of 60-90 min. LPC at final concentrations above 30 muM also caused inhibition of ADP-, collagen-, and thrombin-induced aggregation and collagen- and thrombin-induced release of serotonin in suspensions of rabbit, pig, or human platelets. With washed platelets, the inhibitory effect not only rapidly disappeared but was followed by transient potentiation of aggregation and serotonin release. This potentiating effect of LPC was most pronounced when thrombin was used as stimulus. Both inhibition and potentiation were observed at concentrations of LPC that did not cause a significant change in platelet shape or loss from platelets of lactic dehydrogenase. Inhibition and potentiation were also observed when platelets were added to suspending medium containing LPC, although considerably higher concentrations of LPC were required under these conditions. Potentiation was not observed when LPC was added to citrated or heparinized rabbit or human PRP or to washed rabbit platelets suspended in a medium containing 4% bovine serum albumin. It seemed likely that some or all of the observed effects of LPC on platelet function were due to structural modification of the platelet membrane insufficient to result in gross membrane damage or platelet lysis. In addition, the results of experiments using 14C-LPC seemed to indicate that the observed potentiating effect of LPC on platelet function may be related to its rapid uptake and metabolism by the platelets.
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PMID:Inhibition and potentiation of platelet function by lysolecithin. 83 Mar 68

Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p less than 0.001), adenosine diphosphate-(less than 0.001), collagen- (p = 0.01), and thrombin- (p less than 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels greater than 250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.
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PMID:Platelet thrombopathy in asthmatic patients with elevated immunoglobulin e. 83 79


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