What question did this study set out to answer?

To delineate the molecular mechanisms and signaling pathways that govern thromboxane A2 receptor-stimulated platelet secretion and irreversible aggregation.

August 1, 2003Journal of Biological ChemistryOpen Access

Two Waves of Platelet Secretion Induced by Thromboxane A2 Receptor and a Critical Role for Phosphoinositide 3-Kinases

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Population

Platelets (including PI3Kgamma knock-out mice models)

Comparison

U46619 with or without PI3K inhibitors, integrin… vs Untreated or wild-type platelets

Design

Preclinical

Authors

LZLI Zhen-yuXinxiang Central Hospital GZGuoying ZhangNSF NCAR High Altitude Observatory GBGuy C. Le BretonUniversity of Illinois Chicago

Discussion

Member takes

Overview

PI3Kgamma inhibition may blunt secondary platelet aggregation; leaves open translation to human antiplatelet strategies.

Key Points

To delineate the molecular mechanisms and signaling pathways that govern thromboxane A2 receptor-stimulated platelet secretion and irreversible aggregation.
Stimulated isolated platelets with the stable thromboxane A2 analogue U46619 alongside integrin inhibitor RGDS, P2Y12 receptor antagonists, or PI3K inhibitors.
Assessed platelet secretion, aggregation kinetics, and Akt phosphorylation in wild-type and PI3Kgamma-deficient mouse platelets with or without exogenous ADP supplementation.
U46619 stimulated two successive waves of secretion preceding two distinct waves of aggregation, with the second wave dependent on initial ADP release, integrin outside-in signaling, and P2Y12 Gi pathway activation.
Genetic knockout of PI3Kgamma or chemical PI3K inhibition selectively abolished the second wave of secretion and aggregation, an effect reversed by the addition of exogenous ADP.

Structured PICO

Population

Platelets (including PI3Kgamma knock-out mice models)

Intervention

U46619 (stable TXA2 analogue) with or without PI3K inhibitors, integrin inhibitor RGDS, or P2Y12 receptor antagonist

Comparator

Untreated or wild-type platelets

Outcome

Platelet secretion and aggregationsurrogate

PI3K and integrin outside-in signaling play a central role in inducing a second wave of platelet secretion and irreversible aggregation mediated by Thromboxane A2.

Cite This Study

Zhen-yu et al. (2003) studied this question.

synapsesocial.com/papers/6a8c446f7220baec05bbb9fc https://doi.org/10.1074/jbc.m301838200

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August 1, 2003Journal of Biological ChemistryOpen Access

Two Waves of Platelet Secretion Induced by Thromboxane A2 Receptor and a Critical Role for Phosphoinositide 3-Kinases

View Full Paper

Ask AI

Bookmark

Population

Platelets (including PI3Kgamma knock-out mice models)

Comparison

U46619 with or without PI3K inhibitors, integrin… vs Untreated or wild-type platelets

Design

Preclinical

Authors

LZLI Zhen-yuXinxiang Central Hospital GZGuoying ZhangNSF NCAR High Altitude Observatory GBGuy C. Le BretonUniversity of Illinois Chicago

Discussion

Member takes

Overview

PI3Kgamma inhibition may blunt secondary platelet aggregation; leaves open translation to human antiplatelet strategies.

Key Points

To delineate the molecular mechanisms and signaling pathways that govern thromboxane A2 receptor-stimulated platelet secretion and irreversible aggregation.
Stimulated isolated platelets with the stable thromboxane A2 analogue U46619 alongside integrin inhibitor RGDS, P2Y12 receptor antagonists, or PI3K inhibitors.
Assessed platelet secretion, aggregation kinetics, and Akt phosphorylation in wild-type and PI3Kgamma-deficient mouse platelets with or without exogenous ADP supplementation.
U46619 stimulated two successive waves of secretion preceding two distinct waves of aggregation, with the second wave dependent on initial ADP release, integrin outside-in signaling, and P2Y12 Gi pathway activation.
Genetic knockout of PI3Kgamma or chemical PI3K inhibition selectively abolished the second wave of secretion and aggregation, an effect reversed by the addition of exogenous ADP.

Structured PICO

Population

Platelets (including PI3Kgamma knock-out mice models)

Intervention

U46619 (stable TXA2 analogue) with or without PI3K inhibitors, integrin inhibitor RGDS, or P2Y12 receptor antagonist

Comparator

Untreated or wild-type platelets

Outcome

Platelet secretion and aggregationsurrogate

PI3K and integrin outside-in signaling play a central role in inducing a second wave of platelet secretion and irreversible aggregation mediated by Thromboxane A2.

Cite This Study

Zhen-yu et al. (2003) studied this question.

synapsesocial.com/papers/6a8c446f7220baec05bbb9fc https://doi.org/10.1074/jbc.m301838200

Also Consider

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