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March 21, 2012Platelets

PGE2reverses Gs-mediated inhibition of platelet aggregation by interaction with EP3 receptors, but adds to non-Gs-mediated inhibition of platelet aggregation by interaction with EP4 receptors

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Key result

PGE2 reversed iloprost-induced inhibition of platelet aggregation via the EP3 receptor, but added to inhibition by DN9693 or forskolin via the EP4 receptor.

Population

Platelet-rich plasma obtained from healthy volunteers

Comparison

Prostaglandin E2 with EP3 receptor antagonist or… vs PGE2 without EP receptor antagonists

Design

Preclinical

Authors

JGJacqueline R. GlennAWAnn E. WhiteDIDavid Iyú

Discussion

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Overview

EP3 antagonists may mitigate PGE2 prothrombotic effects; animal platelet data leave open translation to human atherothrombosis.

Structured PICO

P
Population
Platelet-rich plasma obtained from healthy volunteers.
I
Intervention
Prostaglandin E2 (PGE2) with EP3 receptor antagonist (DG-041) or EP4 receptor antagonist (ONO-AE3-208) in the presence of cAMP-raising agents (iloprost, DN9693, or forskolin)
C
Comparator
PGE2 without EP receptor antagonists
O
Outcome
Platelet aggregation in response to adenosine diphosphate (ADP) measured by single platelet counting, and vasodilator-stimulated phosphoprotein (VASP) phosphorylationsurrogate

The prothrombotic effect of PGE2 in the presence of prostacyclin is mediated by EP3 receptors, supporting the potential therapeutic use of EP3 antagonists for atherothrombosis.

Cite This Study

Glenn et al. (2012) studied Healthy volunteers. PGE2 and EP receptor antagonists (DG-041 and ONO-AE3-208) was evaluated on Platelet aggregation and VASP phosphorylation. PGE2 reversed iloprost-induced inhibition of platelet aggregation via the EP3 receptor, but added to inhibition by DN9693 or forskolin via the EP4 receptor.

synapsesocial.com/papers/6a9460bbd1fa461db0c57782https://doi.org/10.3109/09537104.2011.625575
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The role of prostanoid receptors in mediating the effects of PGE<sub>2</sub>on human platelet function2010 · 61 citations
  2. 2Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation2001 · 173 citations
  3. 3The Prostaglandin E2Receptor EP4 Is Expressed by Human Platelets and Potently Inhibits Platelet Aggregation and Thrombus Formation2010 · 87 citations
  4. 4Impaired Responsiveness of Platelets from Patients with Stable Angina Pectoris to Antiaggregating and CyclicAMP-Elevating Effects of Prostaglandin E11995 · 23 citations
  5. 5Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C1993 · 6 citations