Inhibition of Human Platelet Aggregation by Novel 2-Aminochromone Phospholipase C Inhibitors

SummaryWe studied the aggregating effect of different concentrations of phospholipase C (PLC) (extracted from Clostridium perfringens) on human platelet-rich plasma (PRP). PRP was preincubated with PLC for 3 min at 37° C and the platelet aggregation was followed for 10 min. The threshold aggregating concentration (TAG) of PLC was 3-4 U/ml.We also studied the potentiation of PLC with other stimuli on platelet aggregation. Potentiating stimuli, such as arachidonic acid (AA), ADP. Platelet Activating Factor (PAF) and U-46619 (a stable analogue of cyclic endoperoxides) were all used at subthreshold concentrations. We also studied the possible inhibitory effect of aspirin, apyrase, TMQ, a prostaglandin endoper- oxide/thromboxane receptor antagonist and BN-52021, a PAF receptor antagonist. Only aspirin and apyrase were able to reduce aggregation induced by PLC alone and PLC + AA and PLC + ADP respectively. TMQ and BN-52021 were inactive. In ex vivo experiments oral aspirin (500 mg) partially inhibited platelet aggregation induced by PLC alone, PLC + AA and PLC + ADP 2 and 24 h after administration. Aspirin 20 mg for 7 days also reduced aggregation induced by PLC + AA.

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Inhibitory Effect of Staphylokinase on Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649679 ◽

1993 ◽

Vol 70 (05) ◽

pp. 834-837 ◽

Cited By ~ 6

Author(s):

Akira Suehiro ◽

Yoshio Oura ◽

Motoo Ueda ◽

Eizo Kakishita

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Degradation Products ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Effective Concentration ◽

Inhibit Platelet Aggregation ◽

Platelet Suspension ◽

Washed Platelet ◽

Human Platelet Aggregation

SummaryWe investigated the effect of staphylokinase (SAK), which has specific thrombolytic properties, on human platelet aggregation. Platelet aggregation induced with collagen was observed following preincubation of platelets in platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37° C for 30 min. SAK inhibited platelet aggregation in PRP only at the highest examined concentration (1 x 10-4 g/ml). Although SAK did not inhibit platelet aggregation in WP which contained fibrinogen, it did when the platelets had been preincubated with SAK and plasminogen. The most effective concentration in WP was 1 x 10-6 g/ml. The effect could be inhibited by adding aprotinin or α2-antiplasmin. The highest generation of plasmin in the same preincubation fluid was detected at 1 x 10-6 g/ml SAK. We concluded that SAK can inhibit platelet aggregation in WP by generating plasmin and/or fibrinogen degradation products, but is only partially effective in PRP because of the existence of α2-antiplasmin.

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Differential Ability of Agonists to Express Distinct Pools of Fibrinogen (Gpllb/llla) Receptors which Can Mediate the Aggregation of Human Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651035 ◽

1989 ◽

Vol 62 (03) ◽

pp. 955-961 ◽

Cited By ~ 4

Author(s):

Ian S Watts ◽

Rebecca J Keery ◽

Philip Lumley

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Surface Membrane ◽

Blood Platelet ◽

Human Platelets ◽

Membrane Glycoprotein ◽

Platelet Surface ◽

Human Platelet Aggregation ◽

Differential Ability ◽

Blood Platelet Aggregation

SummaryWe have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37° C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.

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Synergism Between Prostacyclin (PGI2) and Prazosin on Human Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657131 ◽

1982 ◽

Vol 47 (01) ◽

pp. 76-76 ◽

Cited By ~ 1

Author(s):

P K Moore

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Human Platelet Aggregation

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Heparin Counteracts the Antiaggregating Effect of Prostacyclin by Potentiating Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657326 ◽

1983 ◽

Vol 49 (02) ◽

pp. 081-083 ◽

Cited By ~ 13

Author(s):

Vittorio Bertelé ◽

Maria Carla Roncaglioni ◽

Maria Benedetta Donati ◽

Giovanni de Gaetano

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Specific Interaction ◽

Inhibitory Effect ◽

Effective Inhibitor ◽

Inhibitory Potency ◽

Human Platelet Aggregation

SummaryIt has recently been reported that heparin neutralizes the inhibitory effect of prostacyclin (PGI2) on human platelet aggregation. The mechanism of this interaction has not yet been unequivocally established. We present here evidence that heparin (Liquemin Roche) does not react directly with PGI2 but counteracts its inhibitory effect by potentiating platelet aggregation. In the absence of heparin, PGI2 was a less effective inhibitor of platelet aggregation induced by the combination of ADP and serotonin than by ADP alone. Moreover, the inhibitory effect of PGI2 was similarly reduced when increasing the concentrations of ADP (in the absence of heparin). The lack of a specific interaction between heparin and PGI2 is supported by the observation that, in the presence of heparin, other prostaglandins such as PGD2 and PGE1, and a non-prostanoid compound such as adenosine also appeared to lose their inhibitory potency. It is concluded that heparin opposes platelet aggregation inhibitory effect of PGI2 by enhancement of platelet aggregation.

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