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:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A non-invasive technique for the scintigraphic determination of 111indium-labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 micrograms kg-1 i.v.), collagen (100 micrograms kg-1 i.v.), platelet-activating factor (PAF, 0.1 microgram kg-1 i.v.) or thrombin (18 iu kg-1 i.v.) was used to investigate the platelet-inhibitory effects of endothelin 1 (ET-1) in anaesthetized rabbits in vivo. 2. ET-1 (1 nmol kg-1 i.v.) inhibited ADP-stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide. 3. ET-1 (1 nmol kg-1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin-induced platelet aggregation. 4. Indomethacin (5 mg kg-1 i.v.) abolished the ET-1-induced inhibition of ADP-stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET-1. 5. In conclusion, the data demonstrate that ET-1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti-aggregatory cyclo-oxygenase product, presumably prostacyclin, into the circulation.
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PMID:Endothelin-1 inhibits platelet aggregation in vivo: a study with 111indium-labelled platelets. 218 12

The influence of genetically engineered recombinant hirudin (r-hirudin) on platelet functions was studied. Depending on the concentration, r-hirudin inhibits the thrombin-induced aggregation and 14C-serotonin secretion to the same extent as native hirudin. Comparative studies in blood anticoagulated by r-hirudin, heparin or citrate show a significantly lower spontaneous platelet aggregation in r-hirudinized blood. The extent of the ADP-induced aggregation is nearly the same in r-hirudinized, heparinized or citrated plasma. In r-hirudinized plasma, however, aggregation is reversible. In contrast to heparinized or citrated plasma, adrenaline causes only a very slight aggregation in r-hirudinized plasma. ADP- or adrenaline-induced secretion of 14C-serotonin do not occur in r-hirudinized plasma. The collagen- as well as the PAF-induced aggregation and 14C-serotonin release in hirudinized plasma do not differ significantly from those in heparinized or citrated plasma. r-Hirudin is a suitable anticoagulant for studying platelet functions because it does not produce any alterations in platelet reactions and does not provoke any changes in the ionized calcium concentration in blood.
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PMID:Platelet functions in recombinant hirudin-anticoagulated blood. 236 46

5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid and collagen, without affecting those induced by ADP, PAF and thrombin. This inhibition was reversible and in a concentration-dependent manner. The IC50 of DK and DDK on arachidonate-induced platelet aggregation were calculated to be about 10 and 60 micrograms/ml, respectively. Thromboxane B2 formation caused by arachidonic acid was also suppressed by both antiplatelet agents. DK inhibited the intracellular calcium concentration rised by arachidonic acid, but not that by collagen or thrombin. DK also inhibited the secondary, but not the primary aggregation of human platelet-rich plasma induced by ADP and epinephrine. It is concluded that the antiplatelet effect of both DK and DDK is due to the inhibition of thromboxane A2 formation.
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PMID:Antiplatelet action of dehydrokawain derivatives isolated from Alpinia speciosa rhizoma. 237 15

Effects of cefaclor (3-chloro-7-D-(2-phenyl-glycinamido)-3-cephem-4-carboxylic acid) on PAF, ADP, collagen, endotoxin, and thrombin-induced platelet aggregation were examined in vitro with the use of guinea pig platelet-rich plasma and washed platelets. PAF, even at concentrations lower than its minimum effective concentration, enhanced ADP- or endotoxin-induced platelet aggregation and prolonged the time to attain the maximum aggregation. PAF also enhanced collagen-induced platelet aggregation and shortened the lag time. Cefaclor (CCL) inhibited the PAF, ADP or thrombin induced platelet aggregation and shortened their maximum aggregation times at higher concentrations such as 300 micrograms/ml or more. CCL also inhibited the collagen-induced platelet aggregation and prolonged the lag time, but showed no effect on endotoxin-induced platelet aggregation. The effect of CCL was almost the same as that of latamoxef (LMOX). CCL and LMOX, however, showed no effect on cellular Ca2+ increase produced by PAF, ADP, or thrombin, suggesting that the inhibitory effect of CCL and LMOX on platelet aggregation is caused by the inhibition of fibrinogen binding to the glycoprotein IIb/IIIa complex.
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PMID:[Effect of cefaclor on guinea pig platelet aggregation in vitro]. 237 85

In summary, the present study documents that platelet aggregation triggered by thrombin, ADP, collagen and PAF both in vivo and in vitro, was prevented by SV-IV in a dose-dependent manner. Only platelet aggregation by AA was not affected by the protein, thus suggesting a possible involvement of PLA2 inhibition in the molecular mechanism at the basis of SV-IV anti-thrombotic effect.
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PMID:In vivo and in vitro inhibition of platelet aggregation by SV-IV, a major protein secreted from the rat seminal vesicle epithelium. 239 Jan 13

Agonists such as thrombin, PAF (platelet-activating factor) and ADP are known to cause a larger elevation in [Ca2+]i in quin2-loaded platelets in the presence of extracellular Ca2+ than in its absence. The simplest interpretation of these observations is that in the presence of extracellular calcium there is an influx component across the cell surface. In the presence of Mn2+, a divalent cation which is known to avidly bind to quin2 and to quench its fluorescence, the agonists produce a small initial rise in quin2 fluorescence followed by a decrease in fluorescence to well below the resting level. The result indicates entry of Mn2+, presumably through some form of receptor-operated Ca2+ channel.
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PMID:Agonists stimulate divalent cation channels in the plasma membrane of human platelets. 240 21

A monoclonal antibody named TM60, which inhibited both thrombin- and ristocetin-induced platelet aggregations, was obtained by hybridoma technique. TM60 inhibited binding of von Willebrand factor to platelets under the presence of ristocetin. The subclass of TM60 was IgG2a. TM60 did not inhibit ADP-, collagen-A-23187-, arachidonic acid- and PAF-induced platelet aggregations, but inhibited polylysine-, polybrene- and cationized ferritin-induced platelet aggregations. ATP-release from platelets induced by thrombin was also inhibited by TM60. Immunoprecipitation and SDS-PAGE experiments demonstrated that TM60 recognized an epitope on GPIb whose molecular weight was 165,000 under non-reduced and 145,000 under reduced conditions.
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PMID:Monoclonal antibody to glycoprotein Ib inhibits both thrombin- and ristocetin-induced platelet aggregations. 241 61

The role of membrane potential in the activation of human platelets by thrombin, ADP and PAF was assessed, using the fluorescent probe diSC3(5). Thrombin, ADP and PAF transiently depolarised the platelet membrane by 6-8 mV from its resting level (-70 mV). This depolarisation had a similar time course to that of shape change. The ionophores valinomycin and gramicidin hyperpolarised and depolarised the platelets respectively but did not activate them. In contrast, exposure of platelets to high K+ media both depolarised and caused them to change shape. Removal of Na+ from the suspension media abolished the depolarisation induced by thrombin, ADP and PAF but the platelets under these conditions were still capable of changing shape and aggregating. This result indicates that the observed depolarisation depends on Na+ fluxes. Amiloride or tetrodotoxin did not mimic the effect of Na+ removal suggesting that any Na+ movement involved does not go through the classic "Na+ channel". Thrombin, ADP and PAF still depolarised the platelet membrane in the absence of added Ca++. Under these conditions, however, the membrane did not repolarise. It is evident that all three agents, thrombin, ADP and PAF, change the membrane potential of human washed platelets through a similar mechanism and this change seems to be a consequence of stimulus-receptor interaction (and platelet activation?). A causal relationship however between these events cannot be clearly shown.
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PMID:Platelet membrane potential: simultaneous measurement of diSC3(5) fluorescence and optical density. 241 25

The evaluation of agents inhibiting platelet function is difficult because, in addition to primary aggregation by thrombin, there are three amplification loops involving respectively arachidonate, ADP and PAF-acether (platelet activating factor). Each amplification loop seems eventually to act via a common pathway: the mobilization of calcium ions from the dense tubular system into the cytoplasm. Inhibition of this mobilization would prevent platelet aggregation by any agonist. This could be an ideal step with which to intervene pharmacologically. An intracellular increase in cAMP reduces cytoplasm calcium levels and therefore counteracts the effect of whatever agonist is used (Vermylen et al, 1982, 1983; Verstraete et al, 1985). Depending on the pro-aggregatory stimulus, the relative importance of a given pathway of platelet activation may shift. There is also uncertainty about which pathway of platelet activation predominates in a given clinical condition. The second problem relates to the pharmacology of the ideal drug for the inhibition of platelet function. It is very difficult to delineate the desired profile of such a drug considering the properties of the various compounds presently being studied (see Table 1). Prolongation of a shortened platelet survival in man was considered to be one of the key markers of an anti-aggregatory agent; this characteristic was found to be present after administration of sulphinpyrazone, clofibrate, ticlopidine, suloctidil, dipyridamole (in patients with artificial heart valves) and dipyridamole (in patients with venous thrombosis). The protective antithrombotic effect is most clearly demonstrated for aspirin; it is rather surprising that this drug does not prolong the shortened platelet survival in man, not even in those clinical conditions in which it effectively prevents thromboembolism.
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PMID:Pharmacology of the interaction between platelets and vessel wall. 242 24

gamma-Thrombin stimulated release of [3H]arachidonic acid ([3H]AA) accompanied by a significant production of PAF and lyso-PAF by rabbit platelets. These responses, which reflect PLA2 activation, were observed after a prolonged lag and to a lower extent when compared to those induced by alpha-thrombin which evoked a much higher elevation in intracellular calcium. This elevation together with [3H]AA release were markedly reduced by EDTA. However, addition of ionophore A23187 enhanced the release of [3H]AA by gamma-thrombin to the levels similar to those of alpha-thrombin. We conclude that gamma-thrombin is able to activate PLA2 and suggest that calcium influx may be a limiting factor for this activation.
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PMID:Gamma-thrombin-induced phospholipase A2 activation in rabbit platelets: comparison with alpha-thrombin. 250 60


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