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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Philipose, S; Konya, V; Sreckovic, I; Marsche, G; Lippe, IT; Peskar, BA; Heinemann, A; Schuligoi, R.
The Prostaglandin E2 Receptor EP4 Is Expressed by Human Platelets and Potently Inhibits Platelet Aggregation and Thrombus Formation.
Arterioscler Thromb Vasc Biol. 2010; 30(12): 2416-2423.
Doi: 10.1161/ATVBAHA.110.216374
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- Führende Autor*innen der Med Uni Graz
- Heinemann Akos
- Sonia Philipose Sonia Philipose
- Co-Autor*innen der Med Uni Graz
- Konya Viktoria
- Lippe Irmgard Theresia
- Marsche Gunther
- Peskar Bernhard
- Schuligoi Rufina
- Sreckovic Ivana
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- Abstract:
- Objective-Low concentrations of prostaglandin (PG) E-2 enhance platelet aggregation, whereas high concentrations inhibit it. The effects of PGE(2) are mediated through 4 G protein-coupled receptors, termed E-type prostaglindin (EP) receptor EP1, EP2, EP3, and EP4. The platelet-stimulating effect of PGE(2) has been suggested to involve EP3 receptors. Here we analyzed the receptor usage relating to the inhibitory effect of PGE(2). Methods and Results-Using flow cytometry, we found that human platelets expressed EP4 receptor protein. A selective EP4 agonist (ONO AE1-329) potently inhibited the platelet aggregation as induced by ADP or collagen. This effect could be completely reversed by an EP4 antagonist, but not by PGI(2), PGD(2), and thromboxane receptor antagonists or cyclooxygenase inhibition. Moreover, an EP4 antagonist enhanced the PGE(2)-induced stimulation of platelet aggregation, indicating a physiological antiaggregatory activity of EP4 receptors. The inhibitory effect of the EP4 agonist was accompanied by attenuated Ca2+ flux, inhibition of glycoprotein IIb/IIIa, and downregulation of P-selectin. Most importantly, adhesion of platelets to fibrinogen under flow and in vitro thrombus formation were effectively prevented by the EP4 agonist. In this respect, the EP4 agonist synergized with acetylsalicylic acid. Conclusion-These results are suggestive of EP4 receptor activation as a novel antithrombotic strategy. (Arterioscler Thromb Vasc Biol. 2010;30:2416-2423.)
- Find related publications in this database (using NLM MeSH Indexing)
- Aspirin - pharmacology
- Blood Coagulation - drug effects
- Blood Platelets - drug effects
- Calcium - metabolism
- Dinoprostone - metabolism
- Dose-Response Relationship, Drug -
- Fibrinogen - metabolism
- Fibrinolytic Agents - pharmacology
- Flow Cytometry -
- Humans -
- Methyl Ethers - pharmacology
- Naphthalenes - pharmacology
- P-Selectin - metabolism
- Phenylbutyrates - pharmacology
- Platelet Adhesiveness -
- Platelet Aggregation - drug effects
- Platelet Aggregation Inhibitors - pharmacology
- Platelet Glycoprotein GPIIb-IIIa Complex - metabolism
- Receptors, Prostaglandin E, EP4 Subtype - drug effects
- Thrombosis - blood
- Find related publications in this database (Keywords)
- aspirin
- pharmacology
- platelet receptor blockers
- platelets
- prostacyclin
- prostaglandins
- thromboxanes