13-Azaprostanoic Acid Potentiates Prostacyclin Induced Platelet Deaggregation

1981 ◽  
Author(s):  
L V Parise ◽  
D Venton ◽  
G C Le Breton
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Present Report ◽  
The Other ◽  
Calcium Sequestration ◽  
Significant Difference ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Stimulation Of

13-Azaprostanoic acid (13-APA), a specific thromboxane/endoperoxide receptor antagonist, reverses platelet aggregation stimulated by the endoperoxide analog U46619. The present report demonstrates that 13-APA also potentiates prostacyclin (PGI2) reversal of U46619-induced aggregation. Human platelet rich plasma was aggregated with 3 × 106M U46619. Deaggregation was induced 2 min. sitosequent to the addition of aggregating agent and was measured over a 3 min. period. Concentrations of 13-APA (4 × 10-4M) and PGI2(4 × 10-9M) were chosen such that each agent individually induced approximately 20% deaggregation. Addition of half of the above concentrations of these agents i.e. 2 × 10-4M 13-APA plus 2 × 10-9M PGI2resulted in 62% deaggregation, demonstrating that the observed response was supraadditive. Only 8% deaggregation was induced by 2 × 10-4M 13-APA alone and 0% by 2 × 10-9M PGI2 alone. PGI2 causes platelet deaggregation presumably through elevation of cAMP. 13-APA, however, did not increase cAMP levels even at concentrations of 13-APA as high as 1.2 × 10-3M i.e. 9.8 ± 1.3 pmoles/ml for control and 10.8 ± 1.2 for 13-APA. Nevertheless it is possible that the observed potentiation of deaggregation was the result of 13-APA facilitating PGI2 stimulation of adenylate cyclase. Measurement of cAMP during deaggregation, however, showed no significant difference between treatment with PGI2 alone and treatment with PGI2 plus 13-APA i.e. 11.3 ± 0.4 pmoles/ml for control, 11.4 ± 0.3 pmoles/ml for 13-APA, 16.1 ± 0.5 pmoles/ml for PGI2 and 16.5 ± 0.8 pmoles/ml for PGI2 plus 13-APA. These results clearly establish that 13-APA and PGI2deaggregate platelets by distinctly separate mechanisms. In this regard we propose that PGI2 causes platelet deaggregation by stimulating intraplatelet calcium sequestration through a cAMP dependent process. 13-APA, on the other hand, blocks the ability of U46619 to mobilize intraplatelet calcium. The combination of these two mechanisms presumably results in the observed potentiation of deaggregation.

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.

Dependence of Human Platelet Functional Responses on Divalent Cations: Aggregation and Secretion in Heparin- and Hirudin-Anticoagulated Platelet-Rich Plasma and the Effects of Chelating Agents

1981 ◽  
Vol 45 (02) ◽  
pp. 173-179 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss
Keyword(s):  
Platelet Aggregation ◽  
Chelating Agents ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Divalent Cations ◽  
Normal Subjects ◽  
Concentration Addition ◽  
Functional Responses ◽  
Induced Aggregation

SummaryThe dependence of ADP- and epinephrine-induced platelet aggregation and secretion on extracellular divalent cations was examined by quantitating these responses in citrate-, heparin-, and hirudin-anticoagulated platelet-rich plasma. ADP-induced 14C-5HT secretion in heparin-PRP and hirudin-PRP was generally decreased, relative to that in citrate-PRP, without corresponding reductions in aggregation, whereas in response to epinephrine, both aggregation and secretion were decreased in heparin-PRP, and abolished in hirudin-PRP. In heparin-PRP, but not in hirudin-PRP, the degree to which these responses were altered was highly variable among normal subjects, and was dependent on the anticoagulant concentration. Addition of citrate restored the extent of ADP-induced secretion and of epinephrine-induced aggregation and secretion in heparin-PRP to that observed in citrate-PRP, and increased the extent of ADP-induced secretion in hirudin-PRP. Addition of EDTA or EGTA, however, had no effect on ADP-induced secretion in heparin-PRP. These results suggest that ADP-induced aggregation and secretion, as well as responses to ADP vs. epinephrine, have different dependencies on extracellular or surface-bound divalent cations. The variable responses observed in heparin-PRP may reflect direct interactions of heparin with platelets, and this variability may account for the conflicting results of previous studies.

Platelet Reactions and Immune Processes

1971 ◽  
Vol 25 (01) ◽  
pp. 086-097 ◽  
Author(s):  
F Jobin ◽  
F Lapointe ◽  
F Gagnon
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Light Chains ◽  
Marked Enhancement

SummaryWe have studied the effect of IgG, IgA, IgM, lambda light chains, Fc fragments, heat-aggregated gammaglobulin, albumin and fibrinogen on the interaction of latex, Kaolin, celite or bentonite particles with human platelet-rich plasma.1. Marked enhancement of platelet aggregating activity was produced by preincubating these particles with IgG at an appropriate concentration. Excess IgG abolished this platelet aggregating property.2. Platelet aggregation could also be induced by betamethasone acetate particles. The latter and IgG-coated latex, Kaolin or bentonite particles were inhibited by chymotrypsin substrates and inhibitors.3. Heat-aggregated IgG produced platelet aggregation in platelet-rich plasma only when adsorbed onto (Kaolin) particles.4. Results obtained with fibrinogen-coated Kaolin suggest that the particles thus acquired a slightly increased platelet clumping activity.5. The other proteins studied failed to enhance the platelet aggregating activity of Kaolin particles, and could even inhibit the formation of IgG-coated Kaolin particles able to readily aggregate platelets.

The Effect of Neuraminidase on Platelet Aggregation Induced by ADP, Norepinephrine, Collagen or Serotonin

1972 ◽  
Vol 28 (02) ◽  
pp. 221-227 ◽  
Author(s):  
James W. Davis ◽  
Kenneth T. N. Yue ◽  
Phyllis E. Phillips
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Acetylneuraminic Acid ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
Second Phases ◽  
Induced Aggregation

SummaryIncubation of human platelet-rich plasma (PRP) with neuraminidase enhanced platelet aggregation induced by adenosine diphosphate (ADP), norepinephrine, collagen or serotonin. Both first and second phases of ADP- and norepinephrine -induced aggregation were enhanced. In two plasmas a second phase of ADP-induced aggregation occurred after incubation with neuraminidase, but not in the control preparations. In one plasma a second phase of serotonin-induced platelet aggregation occurred after incubation with neuraminidase. The incubation of PRP with exogenous N-acetylneuraminic acid (a product of the action of neuraminidase) had no effect on platelet aggregation. A possible explanation of the observed enhancement of platelet aggregation by neuraminidase is that the enzyme may have released sialic acid from platelet membranes and thereby reduced their net negative surface charge.

Interaction between ATP and catecholamines in stimulation of platelet aggregation

2003 ◽  
Vol 284 (2) ◽  
pp. H619-H625 ◽  
Author(s):  
Alex V. Birk ◽  
Endri Leno ◽  
Hugh D. Robertson ◽  
Victoria M. Bolotina ◽  
Hazel H. Szeto
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Endothelial Damage ◽  
Clinical Implications ◽  
Induce Platelet Aggregation ◽  
Intracellular Ca ◽  
Dose Dependent ◽  
Stimulation Of

Platelets, on activation by endothelial damage, release ADP, ATP, serotonin, epinephrine, and norepinephrine. Although ATP is known to augment the action of norepinephrine in cardiovascular and endocrine systems, the possible interaction between ATP and catecholamines in regulation of platelet reactivity has not been reported. The addition of ATP (1–5 μM) to human platelet-rich plasma did not induce platelet aggregation; however, it selectively augmented the aggregatory response to norepinephrine and epinephrine, but not to serotonin. This potentiating action of ATP was dose dependent and was not due to contamination by, or hydrolysis to, ADP. The action of ATP was blocked by 10 μM of adenosine 3′-phosphate 5′-phosphosulfate, a selective P2Y1receptor antagonist. ATP alone did not cause release of intracellular Ca2+, but produced a significant Ca2+response in the presence of norepinephrine. In contrast, the P2X1receptor agonists P1,P6-diadenosine-5′ hexophosphate and α,β-methylene-ATP had no effect on norepinephrine-induced platelet aggregation even when added at 100 μM. This synergistic interaction between ATP and norepinephrine in stimulating platelet aggregation may have significant clinical implications and suggests a prothrombotic role for ATP in stress.

scholarly journals The Effect of Imidazole on Human Platelet Aggregation

Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 417-421 ◽  
Author(s):  
JAMES W. DAVIS ◽  
PHYLLIS E. PHILLIPS
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Glass Bead ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Platelet Function Tests ◽  
Human Platelet Aggregation ◽  
Function Tests ◽  
Induced Aggregation

Abstract Since imidazole buffers have been used in platelet function tests and the compound has been reported to alter several biochemical activities of platelets, it seemed important to determine whether imidazole influenced platelet aggregation. ADP-induced, collagen-induced, and norepinephrine-induced platelet aggregations were tested in platelet-rich plasma by turbidimetric techniques. Glass bead-induced platelet aggregation in whole blood was tested by a method dependent upon platelet counts. Imidazole, in concentrations of 5mM or less, inhibited aggregation induced by each of these four agents and had negligible effect on the pH of platelet-rich plasma. The second phase of both ADP- and norepinephrine-induced aggregation was inhibited or abolished by imidazole, and 5mM imidazole also inhibited the first phase of norepinephrine-induced aggregation. As little as 0.5 mM imidazole inhibited collagen-induced aggregation in some plasmas. Imidazole appears to be unsuitable for use as a buffer in platelet function tests.

Some Characteristics of Mouse Platelet Aggregation and a Comparison of the Activity of a Range of Compounds in Mouse and Human Platelet-Rich Plasma in Vitro

1981 ◽  
Vol 45 (01) ◽  
pp. 001-005 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Similar Activity ◽  
Reversible Aggregation ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Induced Aggregation

SummaryCollagen-induced platelet aggregation in mouse citrated platelet-rich plasma (PRP) was associated with 5-hydroxytryptamine (5-HT) release and degranulation. Adenosine 5’-diphosphate (ADP) induced monophasic and reversible aggregation with no degranulation. Mouse platelets gave no response to adrenaline but changed shape and sometimes aggregated in response to 5-HT. Both amines potentiated the effect of ADP. The respective potencies of prostaglandin E1, papaverine, VK 774, BL 3459 and adenosine as inhibitors of ADP-induced aggregation were similar in mouse and human PRP. Although ticlopidine had similar activity in the two species, aspirin and flurbiprofen were considerably less potent in mouse than human PRP as inhibitors of collagen-induced aggregation. It is suggested that collagen-induced aggregation of mouse platelets in vitro occurs by a mechanism largely independent of arachidonic acid metabolites.

scholarly journals Studies on Ristocetin Induced Platelet Aggregation

1977 ◽  
Author(s):  
R.L. Nachman ◽  
E.A. Jaffe ◽  
B.B. Weksler
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Membrane Surface ◽  
Surface Protein ◽  
Human Platelets ◽  
Glycoprotein I ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

Human platelets washed and fixed in paraformaldehyde aggregate in the presence of the antibiotic ristocetin and normal plasma. This aggregation response is abolished after digestion of the fixed platelets with chymotrypsin. Antisera to fixed washed platelets were produced in rabbits and absorbed with chymotrypsin-treated, fixed washed platelets. Monovalent Fab fragments obtained from the isolated γ-globulin fractions of the antisera blocked ristocetin-induced aggregation of fixed washed platelets in buffer and normal platelets in platelet-rich plasma. By double-antibody immunoprecipitation, it was shown that the antibody which blocked the ristocetin reaction interacted with a platelet membrane surface protein of mol.wt.155,000. Partially purified preparations of membrane glycoprotein I obtained from wheat germ affinity columns block the ristocetin reaction. The results suggest that the glycoprotein I complex on the surface of the human platelet mediates ristocetin-induced von Willebrand factor-dependent platelet aggregation.

scholarly journals Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 1027-1031 ◽  
Author(s):  
AJ Marcus ◽  
LB Safier ◽  
HL Ullman ◽  
KT Wong ◽  
MJ Broekman ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Initial Phase ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Strong Stimulus ◽  
Adp Release ◽  
Irreversible Aggregation ◽  
Induced Aggregation

Abstract AGEPC (PAF), at 1.9 x 10(-8) M or higher, induced concentration- dependent aggregation and release in human platelet-rich plasma. Comparative studies with arachidonate, collagen, ionophore, and ADP suggested that AGEPC was a strong stimulus for platelet aggregation and probably a moderate agonist for release, as well as a relatively weak inducer of TXA2 production. The initial phase of AGEPC-induced aggregation was independent of ADP release and TXA2 formation, since it was not inhibited by ASA, apyrase, or CP/CPK. Whereas irreversible aggregation always required ADP release, TXA2 formation was not essential in each instance. Thus, in several experiments, full aggregation responses took place in AGEPC-stimulated platelets that had been pretreated with ASA. AGEPC-induced release of 5-HT, beta - thromboglobulin and PF-4 occurred in parallel and were inhibited by both apyrase and ASA. Washed human platelets did not respond to exogenous AGEPC in the absence of ADP and did not appear to generate significant quantities of AGEPC upon stimulation with thrombin or ionophore.

Effect of a Moderate Fish lntake on Platelet Aggregation in Human Platelet-Rich Plasma

1988 ◽  
Vol 59 (03) ◽  
pp. 507-513 ◽  
Author(s):  
A C v Houwelingen ◽  
A A H M Hennissen ◽  
F Verbeek-Schippersa ◽  
T Simonsen ◽  
A D M Kester ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
International Study ◽  
Control Group ◽  
Platelet Number ◽  
Dietary Fish ◽  
Fish Group ◽  
Induced Aggregation ◽  
Experimental Group

SummaryThis paper describes the results of an international study to investigate the effect of a reasonable amount of dietary fish on platelet aggregation in platelet-rich plasma (PRP) induced by collagen and thrombin. In Maastricht, Tiomsø, and Zeist two groups of healthy male volunteers were given a daily dietary supplement consisting of 135 g of canned mackerel paste (experimental group, n = 40) or meat paste (control group, n = 42) for a 6-week period. Compliance, calculated on the basis of the urinary excretion of lithium, added to the supplements, was about 80%. Platelet number in PRP decreased significantly in the fish group. Collagen-induced platelet aggregation in PRP differed widely between the three centres despite the attempt to use exactly the same conditions. Nonetheless, aggregation decreased significantly in the fish group. The mackerel effect on thrombin-induced aggregation was inconsistent.

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