Dipyridamole (D) Reduces the Effectiveness of Prostaglandin (PG) I2. PGD2 and PGE1 as Inhibitors of Platelet Aggregation in Human Platelet-Rich Plasma (PRP)

Normal Humans ◽

The Mean

The effectiveness and the mechanism of action of D as an anti-thrombotic agent has been controversial. It has been proposed that D works by potentiating the inhibitory activity of "circulating" PGE2 on platelet aggregation by inhibiting platelet phosphodiesterase activity. To determine whether such potentiation exists in normal humans we studied inhibition of aggregation by the PGs in PRP before and 90 mln after the ingestion of D (100 mg). As expected, we found that the threshold aggregating concentrations of ADP, collagen and arachidonic acid (AA) were unchanged after the ingestion of D. Unexpectedly, the threshold inhibitory concentration of each PG was greater after ingestion of D than before. The mean elevations for PGI2 were 8.8 nM (p<0.05) vs ADP; 9.1 nM(p<0 01) ys collagen; 9.2 nM (p<0.001) vs AA; for FCD2 14.5 nM (p<0.05) vs AA; for PGE, 69 0 nM (p<0.05) vs collagen and 25.9 nM (p<0.05) vs AA. The elevations for PGD2 vs ADP and collagen and for PGE1 vs ADP were not significant. These data do not support the hypothesis that D aces as an anti-thrombotic agent by potentiating the inhibition of platelet aggregation by “circulating” PGIZ. The findings show that ingestion of D Interferes with the inhibitory effect of the PGs and suggest that other mechanisms of action ot D should be investigated.(Supported by the Italian CNR and NIH).

Phospholipase C from Clostridium Perfringens Induces Human Platelet Aggregation in Plasma

10.1055/s-0038-1642761 ◽

1988 ◽

Vol 59 (02) ◽

pp. 236-239 ◽

Cited By ~ 2

Author(s):

Giovanna Barzaghi ◽

Chiara Cerletti ◽

Giovanni de Gaetano

Keyword(s):

Platelet Aggregation ◽

Receptor Antagonist ◽

Phospholipase C ◽

Clostridium Perfringens ◽

Human Platelet ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Platelet Activating Factor ◽

Inhibitory Effect ◽

Thromboxane Receptor Antagonist

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.

Inhibitory Effect of Staphylokinase on Platelet Aggregation

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.

Increased phosphatidic acid and decreased lysophosphatidic acid in response to thrombin is associated with inhibition of platelet aggregation

Biochemistry and Cell Biology ◽

10.1139/o93-064 ◽

1993 ◽

Vol 71 (9-10) ◽

pp. 432-439 ◽

Cited By ~ 17

Author(s):

Jon M. Gerrard ◽

Pauline Robinson ◽

Michael Narvey ◽

Archibald McNicol

Keyword(s):

Platelet Aggregation ◽

Phosphatidic Acid ◽

Lysophosphatidic Acid ◽

Human Platelet ◽

Inhibitory Effect ◽

Phospholipase A ◽

Direct Role ◽

Phosphatidate Phosphohydrolase ◽

Rule Out

Thromboxane A2, produced from the arachidonic acid released from platelet phospholipids by phospholipase A2, stimulates platelet aggregation. It remains unresolved whether additional products of platelet phospholipase A2 might promote aggregation. To address this question, we have used aspirin-treated platelets to block thromboxane A2 formation and studied the influence of the phospholipase A2 inhibitor U10029A on platelet aggregation and secretion in response to thrombin. U10029A at 100 μM markedly inhibited platelet aggregation, but had no effect on platelet secretion. Since this concentration of U10029A effectively blocked lysophosphatidic acid (LPA) formation, LPA was added and found to substantially reverse the inhibitory effect of U10029A in these platelets. Furthermore, the action of U10029A was not due to inhibition of phosphatidate phosphohydrolase because U10029A, unlike propranolol, did not inhibit this enzyme. Although it is not possible to conclusively rule out an effect of U10029A in addition to its inhibition of phospholipase A2, our results reveal that a product of phospholipase A2 other than thromboxane A2 is important for platelet aggregation, but not for secretion in response to thrombin. Our data suggest that this product is LPA. Since the amount of phosphatidic acid (PA) increased dramatically concurrent with inhibition of platelet aggregation, it is safe to conclude that PA has no direct role to promote platelet aggregation in response to thrombin.Key words: lysophosphatidic acid, phosphatidic acid, phospholipase A2, human platelet.

Inhibitory Effect of Hexahydrocurcumin on Human Platelet Aggregation

Natural Product Communications ◽

10.1177/1934578x1200700719 ◽

2012 ◽

Vol 7 (7) ◽

pp. 1934578X1200700 ◽

Cited By ~ 3

Author(s):

Huei-Ping Dong ◽

Rei-Cheng Yang ◽

I-Chun Chunag ◽

Li-Ju Huang ◽

Hsing-Tan Li ◽

...

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Adenosine Diphosphate ◽

Inhibitory Effect ◽

Human Platelet Aggregation

The effects of hexahydrocurcumin on adenosine diphosphate (ADP)-induced human platelet aggregation were studied. Treatment of human platelet-rich plasma with hexahydrocurcumin resulted in an inhibitory effect on platelet aggregation, suggesting the potential of this compound as an anti-atherosclerogenic agent in humans.

Plasmin: A possible physiological modulator of the human platelet adenylate cyclase system

Clinical Science ◽

10.1042/cs0720467 ◽

1987 ◽

Vol 72 (4) ◽

pp. 467-473 ◽

Cited By ~ 10

Author(s):

Serge Adnot ◽

Nicolas Ferry ◽

Jacques Hanoune ◽

Marie-Use Lacombe

Keyword(s):

Platelet Aggregation ◽

Adenylate Cyclase ◽

Human Platelet ◽

Inhibitory Effect ◽

Human Platelets ◽

Cyclase Activity ◽

Adenylate Cyclase Activity ◽

Adenylate Cyclase System ◽

Increased Activity

1. Plasmin was recently reported to inhibit platelet aggregation [1]. We report here on the interaction of plasmin with the adenylate cyclase system of human platelets. Human plasmin caused a dose-and time-dependent increase in adenylate cyclase activity when added to a crude platelet membrane preparation. Both basal and prostaglandin E1-stimulated adenylate cyclase activity doubled in presence of plasmin. This stimulatory activity was shared by papain and α-chymotrypsin, but not by thrombin which displayed a slightly inhibitory effect. 2. Plasmin not only stimulated platelet adenylate cyclase activity, but also suppressed the GTP-dependent α2-adrenergic inhibition, thereby producing a five- to six-fold increased activity measured in the presence of adrenaline and GTP. 3. These effects of plasmin on the adenylate cyclase system were suppressed by the addition of the protease inhibitor leupeptin, and of soybean trypsin inhibitor, indicating that proteolysis mediated these effects. 4. We also examined the adenylate cyclase activity in membranes prepared from intact platelets incubated with increasing doses of plasmin. Incubation of platelets with plasmin concentrations as low as 0.25 mg/ml resulted in an irreversible increase in membrane adenylate cyclase activity and suppression of the adrenaline-mediated inhibition of enzyme activity. 5. These results suggest that the proteolytic stimulating effect of plasmin on the platelet adenylate cyclase system may account for the inhibition of platelet aggregation.

Free Platelet Count and Size Distribution During C1q Inhibition of Collagen-Induced Platelet Aggregation

10.1055/s-0038-1645955 ◽

1987 ◽

Vol 58 (02) ◽

pp. 682-685 ◽

Cited By ~ 3

Author(s):

Gyorgy Csako ◽

Eva A Suba

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Light Transmission ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Lag Phase ◽

Large Platelet ◽

Median Volume ◽

Platelet Aggregates ◽

The Mean

SummaryElectronic free platelet counting was more sensitive than turbidimetry to detect collagen-induced platelet activation in human platelet-rich plasma. Purified human Clq exhibited a greater inhibitory effect on collagen-induced platelet aggregation in turbidimetry than free platelet counting. Because the change from small to large platelet aggregates is responsible for the continuing increase in light transmission, Clq was likely more capable of blocking the formation of large platelet aggregates than the formation of small aggregates from single platelets. The iattr uf change by cullagcn in light tiansmissiun and fiec platelet count was reduced in the presence of Clq but the timing of the peak response remained the same. Electronic platelet sizing revealed that the volume of single platelets transiently increased during the turbidimetric “lag phase”. The mean, mode and median volume of the remaining free platelets then decreased, suggesting a selective loss of large, functionally more active platelets and/or platelet degranulation. Clq had no effect on the volume increment during the “lag phase”, but reduced the subsequent fall in the volume of free platelets.

3’5’-Adenosine Diphosphate (3′5′ADP):A Physiological Inhibitor of Platelet Aggregation and Platelet Release Reaction

10.1055/s-0039-1680423 ◽

1977 ◽

Author(s):

K. Subbarao ◽

K. Jaya

Keyword(s):

Platelet Aggregation ◽

Coenzyme A ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Serotonin Release ◽

Dependent Manner ◽

Release Reaction ◽

Vitro Effect ◽

Aggregation Of Platelets

Certain analogues of adenosine have been shown to inhibit ADP-induced platelet aggregation. We therefore studied the in vitro effect of 3′5′ADP and coenzyme A on human platelet aggregation and [14C]-serotonin release reaction induced by the addition of ADP, thrombin, collagen and epinephrine to human platelet rich plasma (PRP). It was found that coenzyme A Li3·2H2O at a concentration of 0.12 mM strongly inhibited ADP-induced platelet aggregation of PRP but did not show similar effect on the aggregation of platelets induced by other aggregating agents. The 3′5′ADP which is a part of coenzyme A structure, on the other hand, inhibited both ADP and thrombin induced platelet aggregation. The extent of inhibition of platelet aggregation by coenzyme A and 3′5′ADP was found to depend upon the concentration of the inhibitor and the incubation time. Whereas 3′5′ADP Li2·3H2O at a concentration of 10 μM produced about 70% inhibition of ADP-induced platelet aggregation of human PRP, total inhibition of thrombin induced platelet aggregation was observed when platelets were incubated with 60 μM of 3′5′ADP. The 3′5′ADP also inhibited the [14C]-adeonsine uptake by platelets in a concentration dependent manner. The inhibitory potency of 3′5′ADP on platelet aggregation was found to be 10-fold higher than that of N6-2′-0-dibutyryl-cyclic 3′5′-adenosine monophosphate. The inhibition of platelet aggregation by coenzyme A and 3′5′ADP was always accompanied by the inhibition of [14C]-serotonin release reaction. If coenzyme A and 3′5′ADP are indeed physiological inhibitors of platelet aggregation, then aggregation of platelets should depend on metabolic events that regulate the concentration of these agents in blood.

Effects of N-(2-Diethylaminoethyl)-N-(2-hydroxy- 2-phenylethyl)-2,5-dichloroaniline (AN 162) on Platelet Function and Blood Coagulation

Inhibition Of Platelet Aggregation

10.1055/s-0038-1653710 ◽

1971 ◽

Vol 26 (03) ◽

pp. 576-587

Author(s):

R. D Mac Kenzie ◽

T. R Blohm

Keyword(s):

Platelet Aggregation ◽

Blood Clotting ◽

Platelet Rich Plasma ◽

Adenosine Diphosphate ◽

Inhibitory Effect ◽

Clotting Time ◽

Clotting Factors ◽

Platelet Factor ◽

SummaryWhen AN 162 was added to human citrated platelet-rich plasma at 30-300 µg/ml, it inhibited platelet aggregation induced by adenosine diphosphate, collagen, and thrombin. When AN 162 was given orally to guinea pigs at 30 to 100 mg/kg, an in vivo inhibitory effect on platelet aggregability was found. Though it activated platelet factor 3, the concentration of AN 162 required for substantial activation was greater than that for inhibition of platelet aggregation. No effect on plasma clotting factors was found at or below 300 µg/ml. Slight prolongation of whole blood clotting time was found in the rat and monkey.

Effect of Adenyl-Cyclase Activators, Phosphodiesterase Inhibitors and Pyridoxal-5-Phosphate on Platelet Aggregation and Adenosine-3’-5’-Cyclic Monophosphate Accumulation

10.1055/s-0038-1661173 ◽

1984 ◽

Vol 52 (02) ◽

pp. 205-209 ◽

Cited By ~ 8

Author(s):

M Zahavi ◽

J Zahavi ◽

V V Kakkar

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Phosphodiesterase Inhibitors ◽

Adenosine Diphosphate ◽

Adenyl Cyclase ◽

Camp Level ◽

Pde Inhibitors ◽

Indirect Activation

SummaryThe effect of prostaglandin E1 (PGE1) and compound BW245C, adenyl-cyclase activators, theophylline, papaverine and dipyridamole, phosphodiesterase (PDE) inhibitors and pyridoxal- 5-phosphate (PALP) on inhibition of platelet aggregation (PA) and platelet c-AMP accumulation was determined in human platelet-rich plasma (PRP) and washed platelets. PGE1 at 280 nM and BW245C at 7.7 nM induced a significant PA inhibition in PRP and washed platelets (though less pronounced by PGE1) concomitant to a very large increase (8-13-fold) in platelet cAMP level both in PRP and washed platelets. At comparable PA inhibition, c-AMP level was not significantly changed by PALP and only moderately (but significantly) increased (2-4.6-fold) by PDE inhibitors. PALP or theophylline potentiated both PGE1 induced platelet c-AMP accumulation and PA inhibition. Yet PALP potentiated theophylline-induced PA inhibition without affecting platelet c-AMP level.Our results indicate that 2 c-AMP pools are presumably present in the platelets, since at comparable c-AMP accumulation PDE inhibitors or BW245C were more effective than PGE1 in PA inhibition in PRP. Morever, this pattern was more pronounced in washed platelets and was also found in the presence of thrombin and adenosine diphosphate which induced a decrease in platelet c-AMP level. The effect of PALP on PA inhibition is presumably mediated by 2 mechanisms: a) a direct effect on the platelet membrane independent from the c-AMP system, b) In the presence of PGE1, the increment in PA inhibition, is through further indirect activation of the adenyl-cyclase. The mechanism of PA inhibition by BW245C in intact platelets, is most probably through activation of adenyl-cyclase. This study emphasize the importance of c-AMP accumulation in the inhibition of PA.

Effects of Halothane on Platelet Function

10.1055/s-0038-1650105 ◽

1980 ◽

Vol 44 (03) ◽

pp. 143-145 ◽

Cited By ~ 19

Author(s):

J Dalsgaard-Nielsen ◽

J Gormsen

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Human Platelets ◽

Halothane Anaesthesia ◽

Transient Impairment ◽

High Concentrations ◽

Uptake And Release ◽

Platelet Functions

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.