Role of cyclic AMP in the inhibition of human platelet aggregation by quercetin, a flavonoid that potentiates the effect of prostacyclin

SummaryHot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A.auricula and A.polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition than produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts on ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2’,5’-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5’-deoxy, 5’-methylthioadenosine (MTA), an antagonist of Ado receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.

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Role of chondroitin 4-sulphate as a receptor for polycation induced human platelet aggregation

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1996.tb16057.x ◽

1996 ◽

Vol 119 (7) ◽

pp. 1447-1453 ◽

Cited By ~ 16

Author(s):

José L. Donato ◽

Sisi Marcondes ◽

Edson Antunes ◽

Marie D. Nogueira ◽

Helena B. Nader ◽

...

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Human Platelet Aggregation

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Effect of auranofin on human platelet aggregation, release of serotonin, and cyclic-AMP formation

Inflammation ◽

10.1007/bf00915896 ◽

1988 ◽

Vol 12 (1) ◽

pp. 107-112 ◽

Cited By ~ 5

Author(s):

Kaj Winther ◽

Peter Oxholm ◽

Henrik Sengel�v

Keyword(s):

Platelet Aggregation ◽

Cyclic Amp ◽

Human Platelet ◽

Human Platelet Aggregation

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Superoxide Dismutase Cooperates with Prostacyclin to Inhibit Platelet Aggregation: a Comparative Study in Washed Platelets and Platelet Rich Plasma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648164 ◽

1991 ◽

Vol 65 (04) ◽

pp. 421-424 ◽

Cited By ~ 16

Author(s):

Daniela Salvemini ◽

Gilberto de Nucci ◽

John R Vane

Keyword(s):

Superoxide Dismutase ◽

Platelet Aggregation ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Inhibit Platelet Aggregation ◽

Relaxing Factor ◽

Human Platelet Aggregation ◽

Endothelium Derived Relaxing Factor ◽

Krebs Buffer

SummaryThe role of superoxide anions (O2 −) in human platelet aggregation in Krebs’ buffer or plasma was investigated. In indome thacin (10 μM)-treated washed platelets superoxide dismutase (SOD; 60 U/ml) or ferricytochrome c (FCC; 70 μM) inhibited platelet aggregation by thrombin but not that by collagen or ADP. In addition, in indomethacin (10 μM)-treated washed platelets, SOD significantly potentiated the anti-aggregatory activity of prostacyclin (PGI2) or iloprost when thrombin but not collagen was used as the aggregating agent. In platelet rich plasma, SOD (60 U/ml) did not inhibit platelet aggregation nor did it potentiate the anti-aggregatory activity of iloprost when ADP, collagen or thrombin were used as aggregating agents. Thus, O2 − participate in the aggregatory activity of thrombin but not collagen or ADP and PGI2 or iloprost, by reducing the sensitivity of platelets to thrombin, co-operate with SOD to inhibit thrombin-induced platelet aggregationThe interpretation of the use of SOD in experiments involving endothelium-derived relaxing factor (NO) is discussed

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Human Platelet Aggregation Without Thromboxane (Tx) Formation

10.1055/s-0038-1652606 ◽

1981 ◽

Author(s):

J Westwick ◽

J B Smith ◽

V V Kakkar

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Human Platelets ◽

Synthesis Inhibitor ◽

Thromboxane Receptor ◽

Human Platelet Aggregation ◽

Thromboxane Receptor Antagonist ◽

Induced Aggregation ◽

Carbocyclic Thromboxane A2

It is not known whether PG endoperoxides have to be converted to TxA2 in order to induce aggregation and secretion We have examined this crucial question by measuring human platelet aggregation, 14C-5HT release and TxB2 formation induced by collagen, arachidonic acid (AA), adrenaline, U46619 and PGH2 in presence of either 1) 1-2-(4-carboxy-phenoxy) ethyl imidazole hydrochloride, a potent and selective thromboxane synthesis inhibitor (TSI) or a carbocyclic thromboxane A2 (CTA) - a so called thromboxane receptor antagonist. TSI, 1.5 to 75μM produced a dose related inhibition (IC50 5μM n=5) of Tx and elevation of PGE2 synthesis in adrenaline (8μM) and collagen (1.5μg/ml) stimulated platelets. When 14C-SHT labelled platelets were stimulated with 4.5μM adrenaline in the presence of 0, 2.5, 15 and 300μM TSI a 35±2.8, 27±0.5, 24.5±5.0% release of 14C-5HT release resulted and a 10014, 9612, 9711 and 9114% of control aggregation occurred. Similarly when human platelets were stimulated with 0.8mMAA a 51±1.4% (mean ±SE) release of 14C-5HT occurred, while in the presence of 15, 75 and 300μM of UK, a 42±0.4, 32±1, 33±3% of 14C-5HT release resulted. Aggregation induced by the PG endoperoxide analogue U46619 (lμM) was not inhibited by 300μM TSI or l00μM indomethacin, although 99.5% inhibition of Tx formation resulted, and 50 to 60% inhibition of 14C-5HT release was produced both by TSI and indomethacin. However CTA (l-3±M) produced a dose related inhibition of both aggregation and release induced by U46619. CTA (l-10μM) was found to produce superimposable dose related inhibition of collagen induced aggregation and secretion of platelets, whether the platelets were pretreated with 300μM TSI, or not.These results suggest that Tx formation is not necessary for human platelet aggregation, although is contributory to 14C-5HT release induced by collagen, adrenaline, AA and U46619.Also caution must be employed when CTA is used to elucidate the role of TxA2, as it appears to be an effective PG endoperoxide antagonist.

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