Human Platelet Aggregation Induced by the Synthetic Endoperoxide Analogue U-46619 is Independent From Secretion, Prostaglandin Production and Extracellular Calcium

1979 ◽  
Author(s):  
G. Di Minno ◽  
L. Bianchi ◽  
G. de Gaetano ◽  
M.J. Silver
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Extracellular Calcium ◽  
Reversible Aggregation ◽  
Human Platelet Aggregation ◽  
Aspirin Ingestion

U-46619 is a stable analogue of cyclic prostaglandin endoperoxides which induces human platelet aggregation independently from nucleotide secretion. We studied platelet aggregation, 14C-5 HT release and malondialdehyde (MDA) production induced by this compound in stirred or unstirred platelet-rich plasma (PRP) samples from 11 healthy volunteers. Each subject was tested both before and 90 min after aspirin ingestion (500 mg). The threshold aggregating concentration (TAC) of U-466l9 ranged between 240 and 900 nM. Aggregation was maximal between 30 and 60 min after venepuncture and was concentration-dependent (60-7, 200nM). At concentrations below the TAC, U-466l9 induced primary reversible aggregation without detectable l4C-5 HT release. At TAC or higher concentrations aggregation and release proceeded as parallel events. Neither MOA production nor intracellular LDH loss could be detected in any of the tested situations. Aspirin ingestion did not modify the above pattern of platelet responses. In unstirred samples l4C - 5 HT release occurred to the same extent as in stirred platelet suspensions. Addition to citrated PRP of Na2 - EDTA did not affect either aggregation or release. It is suggested that aggregation and secretion may be independent, parallel responses of platelet activation by U-466l9 and do not require either extracellular calcium or activation of endogenous arachidonic acid metabolism. (Supported by the Italian CNR and NIH).

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS SYNERGISTICALLY MODULATE TUMOR CELL INDUCED PLATELET AGGREGATION

1987 ◽  
Author(s):  
Bruce W Steinert ◽  
James M Onoda ◽  
Bonnie F Sloane ◽  
John D Taylor ◽  
Kenneth V Honn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase Inhibitors ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitors ◽  
Agonist Concentration

There has been considerable controversy surrounding the ability of inhibitors of arachidonic acid metabolism to concomitantly inhibit tumor cell induced platelet aggregation (TCIPA). Reconciliation of this controversy has been difficult due to the wide variability of experimental conditions (e.g., inhibitor concentration, strength of the inducing agonist).In the present study, we examined the effects of several cyclooxygenaseand lipoxygenase inhibitors on the induction of platelet aggregation by Walker 256 carcinosarcoma (W256) cells. We have previously demonstrated that aggregation of platelet rich plasma (PRP), induced by W256 cells, was initiated via a thrombin dependent mechanism. Platelet aggregation was induced by the addition of W256 cells (75,000-J500,000 cells/cuvette) to rat PRP preincubated with inhibitor(s) or diluent. The strength of the inducing stimulus affected both the degree of aggregation and the production of thromboxane A2 (TXA2) in a dose dependent manner. A weak stimulus (low concentration of W256 cells) produced only a low level of aggregation and low TXA2 production, whereas aggregation induced by a strong stimulus (high concentration of W256 cells) resulted in significant aggregation and increased TXA2 production. Preincubation (5 min., 37°C) of rat PRP with cyclooxygenase inhibitors (e.g., aspirin, indomethacin, ibuprofen) resulted in complete inhibition of platelet aggregation at low agonist concentration (75,000 W256 cells), whereas when a high agonist concentration (500,000 W256 cells) was used to induce aggregation, the inhibitors failed to inhibit TCIPA. The addition of fewer than 50,000W256 cells failed to induce any measurable platelet aggregation in the presence or absence of inhibitors. TCIPA was not affected by lipoxygenaseinhibitors (e.g.,quercetin) alone regardless of agonist concentration. Both cyclooxygenase and lipoxygenase inhibitors, however, were required to significantly inhibit TCIPA induced by high agonist concentration. Compounds which inhibited both the cycloogygenase and lipoxygenase pathways (e.g.,hydroquinone, BW755c) inhibited TCIPA at all agonist concentrations. Nafazatrom failed to inhibit TCIPA consistant with a lack of effect on platelet cyclooxygenase and lipoxygenase. Therefore, we conclude cyclooxygenase (e.g., TXA2) and lipoxygenase (e.g., 12-HETE) products of platelet arachidonic acid metabolism and the strength of the inducingagonist are important criteria in TCIPA. This study may help to clarify the current controversy regarding the inhibition of TCIPA by inhibitors of arachidonic acid metabolism.

scholarly journals Arachidonic Acid Metabolism of Platelet in Diabetes

1977 ◽  
Author(s):  
T. Kurosawa ◽  
T. Tojima ◽  
H. Funayama ◽  
Y. Takahashi ◽  
Y. Shiokawa
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Sodium Citrate ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Arachidonic Acid Metabolism ◽  
Gas Liquid Chromatography ◽  
Glucose Loading ◽  
Freeze Dried

Recent reports have indicated that platelet aggregation is enhanced in some diabetics who have proliferative retinopathy and that platelet function is a altered by glucose loading. But the mechanism is not clarified yet. Arachidonic acid, the precursor of prostaglandin endoperoxide, plays a major role on platelet aggregation. Blood samples were collected with sodium citrate at 0, 30, 60, 120 and 300 minutes after 100 g glucose loading. Platelet-rich plasma was obtained by centrifugation and platelet aggregation was studied photometrically adding ADP. Platelet was obtained by further centrifugation and was kept freeze-dried. Platelet samples were extracted and transesterificated and separated by gas liquid chromatography. The quantitative regulation of arachidonic acid in platelets was measured by the composition ratio of arachidonic acid (C20-4)/linoleic acid (C18-2)=AL index. The results of platelet aggregation after glucose loading were as follows; platelet aggregation was not changed remarkably in normal subjects, but was enhanced at 30 and 60 and suppressed at 120 minutes in diabetics.AL index is as fol lows:prior to glucose loading, AL index of diabetics (4.6 ± 1.2) was higher than that of normal subjects (3.5 ± 0.5). After glucose loading, no significant change was observed in normal subjects, but AL index was increased at 30 (4.8 ± 1.4) and 60 (4.9 ± 1.4) and decreased at 120 minutes (4.1 ± 0.9) in diabetics. The results indicates that there is a certain relationship between quantitative regulation of arachidonic acid in platelet and platelet aggregation and that hyperaggregation may be induced by abnormal prostaglandin metabolism in diabetes.

Inhibitory Effect of Staphylokinase on Platelet Aggregation

1993 ◽  
Vol 70 (05) ◽  
pp. 834-837 ◽  
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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