Platelet Factor 4 and Adenosine Diphosphate Release during Human Platelet Aggregation

SummaryThe release of platelet factor 4 during platelet aggregation was investigated in diabetic patients. We observed an increased release of platelet factor 4 in diabetic patients.The authors suggest that the increased release of platelet factor 4 may play an essential role in pathogenesis of thromboembolic complications in diabetes mellitus.

Download Full-text

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.

Download Full-text

The effects of an ASA-like hydroperoxide compound on adenosine diphosphate induced platelet aggregation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-053 ◽

1984 ◽

Vol 62 (3) ◽

pp. 338-340

Author(s):

J. J. F. Killackey ◽

B. A. Killackey ◽

I. Cerskus ◽

R. B. Philp

Keyword(s):

Platelet Aggregation ◽

Acetylsalicylic Acid ◽

Pharmacological Property ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Second Phase ◽

Release Reaction ◽

Human Platelet Aggregation ◽

Second Phases ◽

Induced Aggregation

A hydroperoxide compound structurally related to acetylsalicylic acid, 3-hydroperoxy-3-methylphthalide, inhibits both the first and second phases of adenosine diphosphate induced, biphasic, human platelet aggregation. This occurs over the same concentration range (0.05–0.5 mM) that acetylsalicylic acid inhibits second phase aggregation and the release reaction only. The complete inhibition of adenosine diphosphate induced aggregation is a unique pharmacological property for an acetylsalicylic-acid-like compound.

Download Full-text

Macrostachyols A-D, oligostilbenes from Gnetum macrostachyum inhibited in vitro human platelet aggregation

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.39 ◽

2021 ◽

Vol 10 (3) ◽

pp. 339-343

Author(s):

Serm Surapinit ◽

Nuttakorn Baisaeng

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Positive Control ◽

Inhibitory Effects ◽

Aggregation Assay ◽

Human Platelet Aggregation ◽

Platelet Aggregation Assay ◽

Inhibitory Activities

Introduction: Gnetum macrostachyum is a known Thai medicinal plant as a source of bioactive oligostilbenes, which possess platelet inhibitory activities. The study aimed to evaluate the in vitro human platelet aggregation inhibitory activities of macrostachyols A-D (compounds 1-4) isolated from the roots of G. macrostachyum. Methods: The in vitro human platelet aggregation assay was assayed with a 96-well microtiter plate format. The well-known aggregating agents were used to investigate the possible mechanism of inhibition, including adenosine diphosphate (ADP), arachidonic acid (AA), thromboxane A2 analog (U-46619), collagen, thrombin, and thrombin receptor-activating peptide-6 (TRAP-6). Results: Compound 1 was more potent than ibuprofen (positive control) on the adenosine diphosphate- induced platelet aggregation assay (P < 0.05). Compound 3 was more potent than 1, 2, and 4 (P < 0.05), but all active oligostilbenes were less potent than the positive control (P < 0.05) on the arachidonic acid-induced platelet aggregation assay. The oligostilbenes 1, 2, 3, and 4 also displayed the inhibitory effects on the U-46619-induced platelet aggregation. The tetrameric stilbenes 1 was the only compound that exhibited inhibitory effects on thrombin-induced platelet aggregation without TRAP-6 mediated platelet aggregation. Conclusion: The findings revealed the inhibitory effects of oligostilbenes on human platelet aggregation through a target-specific experimental design. It suggests that oligostilbenes from this plant might be applied as antiplatelet aggregation agents in platelet hyperreactivity- related diseases.

Download Full-text

Sevoflurane Does Not Inhibit Human Platelet Aggregation Induced by Thrombin

Anesthesiology ◽

10.1097/00000542-200001000-00028 ◽

2000 ◽

Vol 92 (1) ◽

pp. 164-164 ◽

Cited By ~ 14

Author(s):

Shinji Nozuchi ◽

Toshiki Mizobe ◽

Hiroshi Aoki ◽

Noriko Hiramatsu ◽

Kyoko Kageyama ◽

...

Keyword(s):

Platelet Aggregation ◽

Intracellular Calcium ◽

Calcium Concentration ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Calcium Mobilization ◽

Intracellular Calcium Concentration ◽

Human Platelet Aggregation ◽

Tubular System ◽

Cell Signaling Pathways

Background Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation. Methods Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay. Results Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. Conclusions Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.

Download Full-text

Single-Dose Effect of Enteric-Coated Aspirin on Platelet Function and Thromboxane Generation in Middle-Aged Men

Annals of Pharmacotherapy ◽

10.1177/106002809302700401 ◽

1993 ◽

Vol 27 (4) ◽

pp. 405-410 ◽

Cited By ~ 5

Author(s):

Hiroshi Mohri ◽

Takao Ohkubo

Keyword(s):

Single Dose ◽

Platelet Aggregation ◽

Bleeding Time ◽

Adenine Nucleotides ◽

Adenosine Diphosphate ◽

Platelet Factor 4 ◽

Middle Aged ◽

Platelet Factor ◽

Enteric Coated Aspirin ◽

Enteric Coated

OBJECTIVE: To evaluate the effect of a single dose of enteric-coated aspirin (ECA) in three different dosages on platelet function and thromboxane generation in middle-aged men. DESIGN AND METHODS: In a nonblind, nonplacebo-controlled, crossover study, a single dose of ECA (50, 250, or 1000 mg) was given in a tablet form to a group of healthy, middle-aged men. Ten subjects, aged 50–67 years, volunteered to participate in this study. Platelet functions including bleeding time, platelet aggregation, adenine nucleotides, beta-thromboglobulin, platelet factor 4, thromboxane generation, and aspirin measurement were determined. RESULTS: Before ECA ingestion, the intracellular adenine nucleotides (adenosine triphosphate, adenosine diphosphate) were decreased, and both beta-thromboglobulin and platelet factor 4 were increased. These observations suggested that platelets were activated in vivo in middle-aged men. These findings returned to normal within 8 hours after the ingestion of ECA, and maintained normal for at least two days. Bleeding time was significantly prolonged at 8 and 24 hours compared with that before ingestion of ECA 1000 mg (p<0.05). The generation of platelet thromboxane was maximally inhibited by approximately 40 percent in the samples 8 hours after ECA ingestion. Abnormal values of adenine nucleotides, beta-thromboglobulin, and platelet factor 4 returned to normal within 8 hours. Arachidonic acid-induced platelet aggregation was inhibited compared with that before treatment (p<0.01) and the inhibitory effect was maintained for at least three days. Adenosine diphosphate- and epinephrine-induced aggregations were less inhibited than those induced by arachidonic acid. Inhibitory effects of ECA on platelet aggregation were dose dependent. CONCLUSIONS: Our study indicates that platelets are activated in middle-aged men and that a single dose of ECA 50 mg is safe and can inhibit thromboxane synthesis and platelet aggregation. These results suggest that a daily dose of ECA 50 mg may be useful for blocking platelet activation and preventing thrombosis.

Download Full-text

Human Platelet Aggregation In Response To Multiple Agonists In Plasma Anticoagulated With Heparin

10.1055/s-0038-1652597 ◽

1981 ◽

Author(s):

H A Culliver ◽

N G Ardlie

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Adenosine Diphosphate ◽

Human Platelet Aggregation

The lowest concentrations at which epinephrine and vasopressin have been reported to interact positively in causing platelet aggregation in vitro are at least two orders of magnitude greater than the physiological concentrations of these hormones in blood. The aim of this study was to examine the interaction between several agonists of human platelet aggregation. The aggregating agents used were adenosine diphosphate (ADP), epinephrine, norepinephrine, 5-hydroxytryptamine and vasopressin. Platelet-rich plasma (PRP) was prepared from blood anticoagulated with minimal concentrations of heparin in an attempt to more closely reflect the in vivo situation.Aggregation caused by ADP was potentiated by epinephrine at a concentration exceeding the level obtained in circulating blood. When a third agonist (vasopressin) was used in combination with ADP and epinephrine, aggregation was enhanced at concentrations of vasopressin and epinephrine obtained in blood. When used as a fourth agonist norepinephrine and 5-hydroxytryptamine potentiated aggregation at physiological concentrations. The response to multiple agonists was greater in heparinized PRP than citrated PRP. Hirudin decreased the extent of aggregation in heparinized PRP caused by multiple agonists suggesting that thrombin may be involved.Since the concentrations of combined agonists required to induce in vitro platelet aggregation can be obtained in circulating blood these findings may explain why platelet activation occurs in certain pathological states.

Download Full-text

Protease-activated receptors 1 and 4 do not stimulate Gi signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of Gisignaling

Blood ◽

10.1182/blood.v99.10.3629 ◽

2002 ◽

Vol 99 (10) ◽

pp. 3629-3636 ◽

Cited By ~ 126

Author(s):

Soochong Kim ◽

Carolyn Foster ◽

Anna Lecchi ◽

Todd M. Quinton ◽

Dina M. Prosser ◽

...

Keyword(s):

Platelet Aggregation ◽

Adenylyl Cyclase ◽

Signaling Pathways ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Human Platelets ◽

P2y12 Receptor ◽

General Mechanism ◽

Thrombin Receptor ◽

Human Platelet Aggregation

Thrombin is an important agonist for platelet activation and plays a major role in hemostasis and thrombosis. Thrombin activates platelets mainly through protease-activated receptor 1 (PAR1), PAR4, and glycoprotein Ib. Because adenosine diphosphate and thromboxane A2 have been shown to cause platelet aggregation by concomitant signaling through Gq and Gipathways, we investigated whether coactivation of Gq and Gi signaling pathways is the general mechanism by which PAR1 and PAR4 agonists also activate platelet fibrinogen receptor (αIIbβ3). A PAR1-activating peptide, SFLLRN, and PAR4-activating peptides GYPGKF and AYPGKF, caused inhibition of stimulated adenylyl cyclase in human platelets but not in the presence of either Ro 31-8220, a protein kinase C selective inhibitor that abolishes secretion, or AR-C66096, a P2Y12 receptor–selective antagonist; α-thrombin–induced inhibition of adenylyl cyclase was also blocked by Ro 31-8220 or AR-C66096. In platelets from a P2Y12 receptor–defective patient, α-thrombin, SFLLRN, and GYPGKF also failed to inhibit adenylyl cyclase. In platelets from mice lacking the P2Y12 receptor, neither α-thrombin nor AYPGKF caused inhibition of adenylyl cyclase. Furthermore, AR-C66096 caused a rightward shift of human platelet aggregation induced by the lower concentrations of α-thrombin and AYPGKF but had no effect at higher concentrations. Similar results were obtained with platelets from mice deficient in the P2Y12. We conclude that (1)thrombin- and thrombin receptor-activating peptide–induced inhibition of adenylyl cyclase in platelets depends exclusively on secreted adenosine diphosphate that stimulates Gi signaling pathways and (2) thrombin and thrombin receptor-activating peptides cause platelet aggregation independently of Gi signaling.

Download Full-text

Sevoflurane Inhibits Human Platelet Aggregation and Thromboxane A2Formation, Possibly by Suppression of Cyclooxygenase Activity

Anesthesiology ◽

10.1097/00000542-199612000-00027 ◽

1996 ◽

Vol 85 (6) ◽

pp. 1447-1453. ◽

Cited By ~ 69

Author(s):

Hideo Hirakata ◽

Fumitaka Ushikubi ◽

Hiroshi Toda ◽

Kumi Nakamura ◽

Satoko Sai ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Scatchard Analysis ◽

Cyclooxygenase Activity ◽

Human Platelet Aggregation ◽

Induced Aggregation

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

Download Full-text

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642389 ◽

1994 ◽

Vol 71 (01) ◽

pp. 091-094 ◽

Cited By ~ 15

Author(s):

M Cattaneo ◽

B Akkawat ◽

R L Kinlough-Rathbone ◽

M A Packham ◽

C Cimminiello ◽

...

Keyword(s):

Cardiovascular Disease ◽

Platelet Aggregation ◽

Prostaglandin E1 ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Human Platelets ◽

Before And After ◽

Normal Human ◽

Platelet Aggregates ◽

Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Download Full-text