Variable responses of human platelets to synthetic platelet activating factor and their modification by epinephrine

Tsien, Wen-Hui; Ashley, Constance J.; Sheppard, Herbert

doi:10.1016/0049-3848(82)90174-8

Cited by 7 publications

(4 citation statements)

References 7 publications

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“…The effective con centrations of PAF-acether varied largely from one patient to another. This high vari ability in individual sensitivity to PAFacether is a common feature observed by others [5,7], In the present study, submaxi mal aggregations obtained with PAF-acether concentrations were not normally distrib uted and ranged from 0.7 to lOOnM. As a consequence, when the concentrations used before oral administration of Ticlopidine ex ceeded the median value (i.e., 49.6 nM), pa tients were considered as weak responders to PAF-acether and the data were not taken into account.…”

Section: Paf-acether-lnduced Aggregationmentioning

confidence: 88%

Reduced Sensitivity of Human Platelets to PAF-Acether following Ticlopidine Intake

Chignard

Keraly²,

Delautier³

et al. 1989

Pathophysiol Haemos Thromb

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We investigated in 9 patients the effect of a 7-day treatment by Ticlopidine (250 mg b.i.d.) on washed platelets activation by PAF-acether in comparison with adenosine 5′-diphosphate (ADP) and arachidonic acid (AA). Aggregations induced by ADP were totally suppressed upon drug administration. AA-induced aggregations were partly but significantly inhibited (p < 0.05). Responses of platelets to PAF-acether before treatment differed from patient to patient. A paired Student’s test and a two-way analysis of variance showed a significant inhibitory effect of Ticlopidine treatment on PAF-acether-induced aggregation. The inhibitory effect of Ticlopidine or its metabolite(s) was evidenced after platelet washing procedure, suggesting a persistent effect of this drug on platelet after administration of the drug has been stopped.

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Section: Paf-acether-lnduced Aggregationmentioning

confidence: 88%

Reduced Sensitivity of Human Platelets to PAF-Acether following Ticlopidine Intake

Chignard

Keraly²,

Delautier³

et al. 1989

Pathophysiol Haemos Thromb

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“…Platelet-activating factor (Paf-acether, 1-alkyl-2acetyl-sn-glycero-3-phosphorylcholine) is a potential mediator of the activation of various cell types (Vargaftig et al, 1981;Benveniste & Vargaftig, 1983) including platelets (Benveniste et al, 1975;Cazenave et al, 1979). Doubts were raised concerning the relevance of aggregation of human platelets by Paf-acether, since it has been claimed that the release of ADP (the mediator of the first pathway of aggregation) and/or of arachidonic acid (the mediator of the second pathway; Vargaftig & Zirinis, 1973) fully account for aggregation (Marcus et al, 1981;McManus et al, 1981;Tsien et al, 1982;Chesney et al, 1982;Rao et al, 1982;Ostermann et al, 1983). This is an important problem, since if indeed Paf-acether activates human platelets through aspirin-inhibitable mechanisms (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Doubts were raised concerning the relevance of aggregation of human platelets by Paf-acether, since it has been claimed that the release of ADP (the mediator of the first pathway of aggregation) and/or of arachidonic acid (the mediator of the second pathway; Vargaftig & Zirinis, 1973) fully account for aggregation (Marcus et al, 1981;McManus et al, 1981;Tsien et al, 1982;Chesney et al, 1982;Rao et al, 1982;Ostermann et al, 1983). This is an important problem, since if indeed Paf-acether activates human platelets through aspirin-inhibitable mechanisms (i.e.…”

Section: Introductionmentioning

confidence: 99%

Triggering by Paf‐acether and adrenaline of cyclo‐oxygenase‐independent platelet aggregation

Fouque

Vargäftig

1984

British J Pharmacology

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Platelet‐activating factor (Paf‐acether, 1‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphorylcholine) induced full aggregation and a limited release reaction of human platelets in plasma or in blood. Cyclo‐oxygenase inhibition with aspirin only reduced aggregation when induced by threshold amounts of Paf‐acether, whereas higher concentrations surmounted inhibition whether tested in citrated or in heparinized platelet‐rich plasma or blood. Aspirin‐induced inhibition of platelet secretion by Paf‐acether was insurmountable and independent of the anti‐coagulant used. Paf‐acether and adrenaline acted synergistically in inducing aggregation in citrate and in heparin. Aspirin in vitro or after oral ingestion at doses that suppressed aggregation induced by arachidonic acid alone, failed to reduce significantly the synergized aggregation induced by Paf‐acether alone or combined with adrenaline. Twenty‐four hours after the oral ingestion of aspirin, when aggregation by arachidonic acid remained blocked, a slight inhibitory activity on the effect of Paf‐acether noted 4 h after aspirin, had ceased. This was probably accounted for by the synthesis of thromboxane A2 by newly formed platelets, since the in vitro addition of aspirin, or of the thromboxane/endoperoxide receptor inhibitor 13‐azaprostanoic acid caused the 24 h platelets to behave in a manner similar to platelets collected 4 h after aspirin. The α2‐adrenoceptor inhibitor, yohimbine, blocked the direct effect of adrenaline as well as its synergism with Paf‐acether. Since the synergistic effect of Paf‐acether and adrenaline was maintained when thrombin‐degranulated platelets were used, and aspirin remained ineffective against it, it is clear that the augmented platelet responsiveness is not accounted for by the platelet release reaction. Paf‐acether and adrenaline act synergistically and stimulate platelets by cyclo‐oxygenase‐independent mechanisms, which may be relevant in human physiopathological conditions.

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“…This amplification involves activation ofarachidonic acid metabolism and release reaction and is similar to that of other stimuli, particularly ADP [1][2][3][4][5][6]. Contrasting results, however, have been obtained both on the effect of aspirin, a classical inhibitor of arachidonic acid metabolism and of the release reaction, and on the role of released ADP on PAF-induced human platelet aggregation [1-5; 7-12].…”

Section: Introductionmentioning

confidence: 95%

Contribution of ADP to the amplification of primary platelet aggregation by platelet activating factor (PAF): modulatory role of aspirin

1986

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Platelet Activating Factor (PAF)-induced human platelet aggregation in citrated plasma is accompanied by activation of the cyclo-oxygenase pathway and release of intracellular constituents including Adenosine-5'-diphosphate (ADP). Inhibition of the cyclo-oxygenase pathway by aspirin prevented the amplification of primary platelet aggregation induced by threshold concentrations of PAF. Removal of ADP by enzymatic systems had little or no effect on PAF-induced full aggregation, but reversed the aggregating effect of PAF (at 10 times threshold concentrations) on 'aspirinated' platelets. Aspirin also prevented the synergism between PAF and ADP when subthreshold concentrations of both compounds were combined. Similar results were obtained in heparinized platelet-rich plasma. Thus, ADP may amplify the primary response to PAF but its role is modulated by the availability of the cyclo-oxygenase pathway products.

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Variable responses of human platelets to synthetic platelet activating factor and their modification by epinephrine

Cited by 7 publications

References 7 publications

Reduced Sensitivity of Human Platelets to PAF-Acether following Ticlopidine Intake

Reduced Sensitivity of Human Platelets to PAF-Acether following Ticlopidine Intake

Triggering by Paf‐acether and adrenaline of cyclo‐oxygenase‐independent platelet aggregation

Contribution of ADP to the amplification of primary platelet aggregation by platelet activating factor (PAF): modulatory role of aspirin

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