BIOMAT Database Logo BIOMAT Database Logo

The prostaglandin E2 receptor EP4 is expressed by human platelets and potently inhibits platelet aggregation and thrombus formation. 2010

Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitaetsplatz 4, A-8010 Graz, Austria.

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). 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 Ca(2+) 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. CONCLUSIONS These results are suggestive of EP4 receptor activation as a novel antithrombotic strategy.

UI MeSH Term Description Entries
D008738 Methyl Ethers A group of compounds that contain the general formula R-OCH3. Ethers, Methyl
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D010654 Phenylbutyrates Derivatives of 4-phenylbutyric acid, including its salts and esters.
D010973 Platelet Adhesiveness The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces. Adhesiveness, Platelet,Adhesivenesses, Platelet,Platelet Adhesivenesses
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D001777 Blood Coagulation The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot. Blood Clotting,Coagulation, Blood,Blood Clottings,Clotting, Blood
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

Related Publications

Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Circadian nuclear receptor Rev-erbĪ± is expressed by platelets and potentiates platelet activation and thrombus formation.
June 2022, European heart journal,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Selective activation of the prostaglandin E2 receptor subtype EP2 or EP4 leads to inhibition of platelet aggregation.
October 2010, Thrombosis and haemostasis,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin E2 both stimulates and inhibits adenyl cyclase on platelets: comparison of effects on cloned EP4 and EP3 prostaglandin receptor subtypes.
September 1996, Prostaglandins,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin D2 inhibits the aggregation of human platelets.
September 1974, Thrombosis research,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin E2 Inhibits NLRP3 Inflammasome Activation through EP4 Receptor and Intracellular Cyclic AMP in Human Macrophages.
June 2015, Journal of immunology (Baltimore, Md. : 1950),
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Inhibition of platelet aggregation and white thrombus formation by prostaglandin analogue ONO-747.
January 1976, Advances in prostaglandin and thromboxane research,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin E2 strongly inhibits human osteoclast formation.
December 2005, Endocrinology,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin E2 receptor EP4-selective antagonist inhibits lipopolysaccharide-induced cervical ripening in rabbits.
January 2007, Acta obstetricia et gynecologica Scandinavica,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor.
November 2002, The Journal of biological chemistry,
Sonia Philipose, and Viktoria Konya, and Ivana Sreckovic, and Gunther Marsche, and Irmgard T Lippe, and Bernhard A Peskar, and Akos Heinemann, and Rufina Schuligoi
Tripeptide SQL Inhibits Platelet Aggregation and Thrombus Formation by Affecting PI3K/Akt Signaling.
September 2015, Journal of cardiovascular pharmacology,
Copied contents to your clipboard!