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30 Investigation of the action of prostaglandin E2 on human platelets
  1. N J Truss,
  2. T D Warner
  1. The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK

Abstract

Prostaglandin E2 (PGE2) is a product of the COX pathway and its production is believed to be elevated at sites of atherosclerotic lesions. PGE2 does not alter platelet responses by itself, but does modulate responses in the presence of other agonists. Previous studies using knockout mice models found conflicting evidence to studies using human platelets with regard to the receptors that mediate the platelet effects of PGE2. Here we further investigated the effects of PGE2 on platelet aggregation to submaximal agonist stimulation. Platelet rich plasma (PRP) was prepared by centrifugation at 175 g for 15 min. PRP was incubated with the EP3 receptor antagonist, L-798 106 (0.3–30 nM) for 20 min, before addition of PGE2 (0.1–30 μM) and incubation for a further 20 min. Aggregation on 96-well plates was then stimulated by addition of 0.6 μM U46619, followed by reading of absorption over 16 min with shaking between readings. By itself 0.6 μM U46619 caused submaximal aggregation, this was potentiated by PGE2 at concentrations up to 1 μM; concentrations beyond this inhibited aggregation. Pre-treatment with L-798106 significantly reduced the potentiating action of low concentrations of PGE2 on platelet aggregation. For example, in the presence of 0.6 μM U46619 alone aggregation was 37%±12%, in the presence of 0.3 μM PGE2 this increased to 65%±9%, with the further addition of 10 nML-798 106 this was reduced to 40%±5% (n=4). These results indicate that PGE2 has both pro-aggregatory (at lower concentrations) and anti-aggregatory (at higher concentrations) effects upon platelets, and that the EP3 receptor contributes to the potentiating action of PGE2 on human platelet aggregation.

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