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On the Interrelationship of Prostaglandin Endoperoxide G2 and Cyclic Nucleotides in Platelet Function

Hans‐Erik CLAESSON

Kemiska Institutionen II, Karolinska Institutet, Solnavägen 1, S‐104 01 Stockholm, Sweden

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Curt MALMSTEN

Kemiska Institutionen II, Karolinska Institutet, Solnavägen 1, S‐104 01 Stockholm, Sweden

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First published: June 1977
Cited by: 26

Abstract

The prostaglandin endoperoxide G2 caused rapid aggregation and release of ADP and [14C]serotonin in human platelets. Since the presence of the ADP phosphorylating system creatine phosphate creatine phosphokinase markedly inhibited the aggregation caused by the endoperoxide, this effect seemed to be mediated mainly by ADP, which is instantaneously released by the endoperoxide.

The prostaglandin G2 counteracted the increasing effect of prostaglandin E1 on the adenosine 3′:5′‐monophosphate (cAMP) levels in platelet‐rich plasma. This effect of prostaglandin G2 was only observed when ADP was released by the endoperoxide. This finding indicates that the effect of prostaglandin G2 on the cAMP levels in platelet‐rich plasma is principally mediated by ADP. The rapid release of ADP by prostaglandin G2 and the time courses for the effects of the endoperoxide and ADP on the level of cAMP give further evidence for this hypothesis. ADP also caused primary aggregation in the presence of indomethacin, and prostaglandin synthesis inhibitors did not influence the decreasing effect of ADP on the cAMP levels. N2,O2‐Dibutyrylguanosine 3′:5′‐monophosphate did not influence the aggregation and release‐reaction caused by ADP and no changes of the cGMP levels were observed after addition of prostaglandin G2.

Number of times cited: 26

  • , The Role of Heterotrimeric G Proteins in Platelet Activation, Biological Chemistry, 381, 5-6, (2000).
  • , Purification, Cloning, Expression, and Mechanism of Action of a Novel Platelet Aggregation Inhibitor from the Salivary Gland of the Blood-sucking Bug,Rhodnius prolixus, Journal of Biological Chemistry, 275, 17, (12639), (2000).
  • , Molecular Mechanism of Thromboxane A2-induced Platelet Aggregation, Journal of Biological Chemistry, 274, 41, (29108), (1999).
  • , Antiplatelet and antithrombotic effects of organic nitrates, The American Journal of Cardiology, 70, 8, (B18), (1992).
  • , Platelet thromboxane A2/prostaglandin H2 receptors in human volunteers on low doses of aspirin, Biochemical Pharmacology, 40, 7, (1559), (1990).
  • , Binding of thromboxane A2/prostaglandin H2 agonists to human platelets, British Journal of Pharmacology, 91, 1, (223-227), (2012).
  • , Prostaglandins, thromboxanes, and leukotrienes in inflammation, The American Journal of Medicine, 80, 4, (11), (1986).
  • , Prostaglandins, thromboxanes, and leukotrienes in inflammation, Seminars in Arthritis and Rheumatism, 15, 2, (29), (1985).
  • , Arachidonic Acid Metabolism and Inflammation a brief Introduction, Scandinavian Journal of Rheumatology, 13, sup53, (31), (1984).
  • , Prostaglandin H2 directly lowers human platelet cAMP levels, Thrombosis Research, 30, 5, (407), (1983).
  • , Chapter 2 The thromboxanes, Prostaglandins and related substances, 10.1016/S0167-7306(08)60534-7, (45-94), (1983).
  • , Sodium arachidonate induced platelet aggregation is independent of secreted adenosine diphosphate, Thrombosis Research, 31, 5, (747), (1983).
  • , Prostaglandin I2 synthesis and elevation of cyclic AMP levels in 3T3 fibroblasts, Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 618, 3, (399), (1980).
  • , The effect of hypercholesterolaemia on the lipid composition and ability of human platelets to accumulate cyclic AMP, Prostaglandins and Medicine, 5, 6, (457), (1980).
  • , Thromboxane production and platelet aggregation in diabetic subjects with clinical complications, Thrombosis Research, 19, 1-2, (211), (1980).
  • , Inhibition of platelet aggregation and elevation of cyclic-amp levels in platelets by 13,14-dehydro PGI2 methyl ester, Prostaglandins and Medicine, 4, 6, (453), (1980).
  • , Factors Influencing the Response of Human Blood Platelets to Analogues of ADP Which May Act as Partial Agonists at the ADP Receptor, European Journal of Biochemistry, 95, 1, (127-137), (2008).
  • , PROSTAGLANDINS, THROMBOXANES AND PLATELETS, British Journal of Haematology, 41, 4, (453-458), (2008).
  • , Effects of adenosine 3′:5′‐monophosphate and platelet aggregation on thromboxane biosynthesis in human platelets, FEBS Letters, 98, 2, (247-250), (2001).
  • , Prostaglandin Endoperoxides and Thromboxanes: Role in Platelets, Prostaglandins–Immunopharmacology, 10.1016/B978-0-08-023194-5.50017-6, (111-115), (1979).
  • , Platelet Secretion (Release Reaction)-Mechanism and Pharmacology, Prostaglandins–Immunopharmacology, 10.1016/B978-0-08-023194-5.50016-4, (97-109), (1979).
  • , Independence of the cyclic amp-lowering activity of thromboxane a2 from the platelet release reaction, Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 572, 1, (95), (1979).
  • , Factors Affecting the Formation and Actions of Cyclic AMP in Blood Platelets, Prostaglandins–Immunopharmacology, 10.1016/B978-0-08-023194-5.50014-0, (75-85), (1979).
  • , Prostaglandins and Thromboxanes, Proceedings of the 1977 Laurentian Hormone Conference, 10.1016/B978-0-12-571134-0.50010-7, (239-258), (1978).
  • , Elevation of adenosine 3′,5′‐monophosphate levels in 3T3 fibroblasts by arachidonic acid: evidence for mediation by prostaglandin I2 , FEBS Letters, 81, 2, (415-418), (2001).
  • , Inhibition of prostaglandin synthesis in mouse 3T3 fibroblasts and human platelets by substituted phenols, Prostaglandins, 13, 6, (1093), (1977).