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Home / Equine Research Bank / Prostaglandins / Comparison of the effects of prostacyclin (PGI2), prostaglan...
Prostaglandins1978; 16(3); 373-388; doi: 10.1016/0090-6980(78)90216-2

Comparison of the effects of prostacyclin (PGI2), prostaglandin E1 and D2 on platelet aggregation in different species.

Abstract: The activity of prostacyclin (PGI2), PGE1 or PGD2 as inhibitors of platelet aggregation in plasma from human, dog, rabbit, rat, sheep and horse was investigated. Prostacyclin was the most potent inhibitor in all species. PGD2 was a weak inhibitor in dog, rabbit and rat plasma whereas PGE1 and prostacyclin were highly active. Theophylline or dipyridamole potentiated the inhibition of human platelet aggregation by prostacyclin, PGE1 or PGD2. Compound N-0164 abolished the inhibition by PGD2 of human platelet aggregation but did not inhibit the effects of PGE1 or prostacyclin. The results suggest that prostacyclin and PGE1 act on similar sites on platelets which are distinct from those for PGD2.
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Publication Date: 1978-09-01 PubMed ID: 364545DOI: 10.1016/0090-6980(78)90216-2Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study investigates the effectiveness of three types of prostaglandins – prostacyclin (PGI2), PGE1, and PGD2 – in preventing platelet aggregation in various species. The study also explored the potency of other drugs on these prostaglandins.

Research Objective and Methodology

  • The study aimed to understand and compare the activity of three types of prostaglandins: prostacyclin (PGI2), PGE1, and PGD2 as inhibitors of platelet aggregation in plasma from human, dog, rabbit, rat, sheep, and horse.
  • They studied the potency of these prostaglandins as inhibitors and explored the impact of theophylline, dipyridamole, and the compound N-0164 on the prostaglandins’ functions.

Research Findings

  • The study found prostacyclin (PGI2) to be the most potent inhibitor of platelet aggregation in all species examined. This highlights its potential for broad-spectrum use in preventing platelet aggregation in diverse species.
  • PGD2 presented as a weak inhibitor in dog, rabbit, and rat plasma, thus suggesting less effectiveness in these species. PGE1 and prostacyclin, on the other hand, were highly active and effective in these species.
  • The researchers also noticed that the drugs theophylline or dipyridamole augmented the prostaglandins’ inhibition of human platelet aggregation. This indicates the potential of these drugs to elevate the activity and effectiveness of prostaglandins.
  • They found that compound N-0164 abolished the inhibition by PGD2 of human platelet aggregation but did not inhibit the effects of PGE1 or prostacyclin. This suggests that N-0164 may selectively counteract PGD2’s effects but not that of PGE1 or prostacyclin.

Conclusion

  • The study concludes that prostacyclin and PGE1 act on similar sites on platelets, distinct from those for PGD2. This conclusion provides insights into the different mechanisms of these prostaglandins, which could be valuable in medical interventions involving platelet aggregation.

Cite This Article

APA
Whittle BJ, Moncada S, Vane JR. (1978). Comparison of the effects of prostacyclin (PGI2), prostaglandin E1 and D2 on platelet aggregation in different species. Prostaglandins, 16(3), 373-388. https://doi.org/10.1016/0090-6980(78)90216-2

Publication

Prostaglandins
ISSN: 0090-6980
NlmUniqueID: 0320271
Country: United States
Language: English
Volume: 16
Issue: 3
Pages: 373-388

Researcher Affiliations

Whittle, B J
    Moncada, S
      Vane, J R

        MeSH Terms

        • Animals
        • Dipyridamole / pharmacology
        • Dogs
        • Epoprostenol / pharmacology
        • Horses
        • Humans
        • Organophosphonates
        • Organophosphorus Compounds / pharmacology
        • Platelet Aggregation / drug effects
        • Prostaglandin Antagonists / pharmacology
        • Prostaglandins / pharmacology
        • Prostaglandins D / pharmacology
        • Prostaglandins E / pharmacology
        • Rabbits
        • Rats
        • Ristocetin / pharmacology
        • Sheep
        • Species Specificity
        • Theophylline / pharmacology

        Citations

        This article has been cited 56 times.
        1. León Fernández OS, Oru GT, Viebahn-Hänsler R, López Cabreja G, Serrano Espinosa I, García Fernández E. Medical ozone arrests oxidative damage progression and regulates vasoactive mediator levels in elderly patients (60-70 years) with oxidative etiology diseases. Front Physiol 2022;13:1029805.
          doi: 10.3389/fphys.2022.1029805pubmed: 36406985google scholar: lookup
        2. Walker DI, Hart JE, Patel CJ, Rudel R, Chu JH, Garshick E, Pennell KD, Laden F, Jones DP. Integrated molecular response of exposure to traffic-related pollutants in the US trucking industry. Environ Int 2022 Jan;158:106957.
          doi: 10.1016/j.envint.2021.106957pubmed: 34737152google scholar: lookup
        3. Braune S, Küpper JH, Jung F. Effect of Prostanoids on Human Platelet Function: An Overview. Int J Mol Sci 2020 Nov 27;21(23).
          doi: 10.3390/ijms21239020pubmed: 33260972google scholar: lookup
        4. Engevik AC, Kaji I, Goldenring JR. The Physiology of the Gastric Parietal Cell. Physiol Rev 2020 Apr 1;100(2):573-602.
          doi: 10.1152/physrev.00016.2019pubmed: 31670611google scholar: lookup
        5. Giménez-Bastida JA, Boeglin WE, Boutaud O, Malkowski MG, Schneider C. Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation. FASEB J 2019 Jan;33(1):1033-1041.
          doi: 10.1096/fj.201801018Rpubmed: 30096040google scholar: lookup
        6. Crescente M, Menke L, Chan MV, Armstrong PC, Warner TD. Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond). Br J Pharmacol 2019 Apr;176(8):988-999.
          doi: 10.1111/bph.14196pubmed: 29512148google scholar: lookup
        7. Yeung J, Hawley M, Holinstat M. The expansive role of oxylipins on platelet biology. J Mol Med (Berl) 2017 Jun;95(6):575-588.
          doi: 10.1007/s00109-017-1542-4pubmed: 28528513google scholar: lookup
        8. Banerjee D, Mazumder S, Kumar Sinha A. Involvement of Nitric Oxide on Calcium Mobilization and Arachidonic Acid Pathway Activation during Platelet Aggregation with different aggregating agonists. Int J Biomed Sci 2016 Mar;12(1):25-35.
          pubmed: 27127451
        9. Chen ZI, Ai DI. Cardiotoxicity associated with targeted cancer therapies. Mol Clin Oncol 2016 May;4(5):675-681.
          doi: 10.3892/mco.2016.800pubmed: 27123262google scholar: lookup
        10. Riond B, Waßmuth AK, Hartnack S, Hofmann-Lehmann R, Lutz H. Effective prevention of pseudothrombocytopenia in feline blood samples with the prostaglandin I2 analogue Iloprost. BMC Vet Res 2015 Aug 6;11:183.
          doi: 10.1186/s12917-015-0510-xpubmed: 26245701google scholar: lookup
        11. Laidlaw TM, Boyce JA. Platelets in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2015 Jun;135(6):1407-14; quiz 1415.
          doi: 10.1016/j.jaci.2015.02.005pubmed: 26051947google scholar: lookup
        12. Bank S, Jana P, Maiti S, Guha S, Sinha AK. Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction. Sci Rep 2014 Jul 24;4:5804.
          doi: 10.1038/srep05804pubmed: 25055737google scholar: lookup
        13. Ghosh R, Ray U, Jana P, Bhattacharya R, Banerjee D, Sinha A. Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide. PLoS One 2014;9(2):e88639.
          doi: 10.1371/journal.pone.0088639pubmed: 24558405google scholar: lookup
        14. Kataoka N, Satoh T, Hirai A, Saeki K, Yokozeki H. Indomethacin inhibits eosinophil migration to prostaglandin D2 : therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis. Immunology 2013 Sep;140(1):78-86.
          doi: 10.1111/imm.12112pubmed: 23582181google scholar: lookup
        15. Louis L, Bair N, Banjac S, Dweik RA, Tonelli AR. Subdural hematomas in pulmonary arterial hypertension patients treated with prostacyclin analogs [corrected]. Pulm Circ 2012 Oct;2(4):518-21.
          doi: 10.4103/2045-8932.105041pubmed: 23372937google scholar: lookup
        16. Qian H, Luo N, Chi Y. Aging-shifted prostaglandin profile in endothelium as a factor in cardiovascular disorders. J Aging Res 2012;2012:121390.
          doi: 10.1155/2012/121390pubmed: 22500225google scholar: lookup
        17. Song WL, Stubbe J, Ricciotti E, Alamuddin N, Ibrahim S, Crichton I, Prempeh M, Lawson JA, Wilensky RL, Rasmussen LM, Puré E, FitzGerald GA. Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans. J Clin Invest 2012 Apr;122(4):1459-68.
          doi: 10.1172/JCI59262pubmed: 22406532google scholar: lookup
        18. Yamamoto Y, Otani S, Hirai H, Nagata K, Aritake K, Urade Y, Narumiya S, Yokozeki H, Nakamura M, Satoh T. Dual functions of prostaglandin D2 in murine contact hypersensitivity via DP and CRTH2. Am J Pathol 2011 Jul;179(1):302-14.
          doi: 10.1016/j.ajpath.2011.03.047pubmed: 21703412google scholar: lookup
        19. Smyth EM. Thromboxane and the thromboxane receptor in cardiovascular disease. Clin Lipidol 2010 Apr 1;5(2):209-219.
          doi: 10.2217/clp.10.11pubmed: 20543887google scholar: lookup
        20. Shimura C, Satoh T, Igawa K, Aritake K, Urade Y, Nakamura M, Yokozeki H. Dendritic cells express hematopoietic prostaglandin D synthase and function as a source of prostaglandin D2 in the skin. Am J Pathol 2010 Jan;176(1):227-37.
          doi: 10.2353/ajpath.2010.090111pubmed: 20008150google scholar: lookup
        21. Bhattacharyya M, Karmohapatra SK, Bhattacharya G, Bhattacharya R, Sinha AK. The role of leucocytes in the acetyl salicylic acid (aspirin) induced nitric oxide synthesis in the production of interferon-alpha, a potent inhibitor of platelet aggregation and a thrombolytic agent. J Thromb Thrombolysis 2009 Aug;28(2):173-84.
          doi: 10.1007/s11239-008-0283-1pubmed: 18846318google scholar: lookup
        22. Wei G, Kibler KK, Koehler RC, Maruyama T, Narumiya S, Doré S. Prostacyclin receptor deletion aggravates hippocampal neuronal loss after bilateral common carotid artery occlusion in mouse. Neuroscience 2008 Oct 28;156(4):1111-7.
          doi: 10.1016/j.neuroscience.2008.07.073pubmed: 18790018google scholar: lookup
        23. Ragolia L, Hall CE, Palaia T. Post-translational modification regulates prostaglandin D2 synthase apoptotic activity: characterization by site-directed mutagenesis. Prostaglandins Other Lipid Mediat 2007 Feb;83(1-2):25-32.
          doi: 10.1016/j.prostaglandins.2006.09.006pubmed: 17259069google scholar: lookup
        24. Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K, Inui T, Fukumoto N, Eguchi N, Kushi A, Sasai H, Kanaoka Y, Ozono K, Narumiya S, Suzuki K, Urade Y. Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J Neurosci 2006 Apr 19;26(16):4383-93.
          doi: 10.1523/JNEUROSCI.4531-05.2006pubmed: 16624958google scholar: lookup
        25. Nagasaka T, Hiraide M, Sugimoto T, Shindo K, Shiozawa Z, Yokota S. Localization of lipocaline-type prostaglandin D synthase in rat brain: immunoelectron microscopic study. Histochem Cell Biol 2004 Jun;121(6):483-91.
          doi: 10.1007/s00418-004-0658-0pubmed: 15221417google scholar: lookup
        26. Gliki G, Abu-Ghazaleh R, Jezequel S, Wheeler-Jones C, Zachary I. Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-delta and by mobilization of intracellular Ca2+. Biochem J 2001 Feb 1;353(Pt 3):503-12.
          doi: 10.1042/0264-6021:3530503pubmed: 11171046google scholar: lookup
        27. Yoshida T, Ohki S, Kanazawa M, Mizunuma H, Kikuchi Y, Satoh H, Andoh Y, Tsuchiya A, Abe R. Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer. Surg Today 1998;28(7):740-5.
          doi: 10.1007/BF02484622pubmed: 9697269google scholar: lookup
        28. Eguchi Y, Eguchi N, Oda H, Seiki K, Kijima Y, Matsu-ura Y, Urade Y, Hayaishi O. Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients. Proc Natl Acad Sci U S A 1997 Dec 23;94(26):14689-94.
          doi: 10.1073/pnas.94.26.14689pubmed: 9405674google scholar: lookup
        29. Cawello W, Leonhardt A, Schweer H, Seyberth HW, Bonn R, Lomeli AL. Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy volunteers following intravenous infusion. Br J Clin Pharmacol 1995 Sep;40(3):273-6.
          doi: 10.1111/j.1365-2125.1995.tb05784.xpubmed: 8527291google scholar: lookup
        30. Matthews JS, Jones RL. Potentiation of aggregation and inhibition of adenylate cyclase in human platelets by prostaglandin E analogues. Br J Pharmacol 1993 Feb;108(2):363-9.
          doi: 10.1111/j.1476-5381.1993.tb12810.xpubmed: 8448586google scholar: lookup
        31. Ueno Y, Shigenobu K, Nishio S. Effects of beraprost on the transmembrane potentials of guinea-pig ventricular muscles during normoxia and hypoxia-reoxygenation. Br J Pharmacol 1993 Aug;109(4):1014-9.
          doi: 10.1111/j.1476-5381.1993.tb13722.xpubmed: 8401913google scholar: lookup
        32. Clifford PC, Martin MF, Sheddon EJ, Kirby JD, Baird RN, Dieppe PA. Treatment of vasospastic disease with prostaglandin E1. Br Med J 1980 Oct 18;281(6247):1031-4.
          doi: 10.1136/bmj.281.6247.1031pubmed: 7427564google scholar: lookup
        33. Mukhammedov A, Suvorov AV. Effect of sympathectomy on platelet aggregation and blood coagulation in rats. Experientia 1980 Jul 15;36(7):849-50.
          doi: 10.1007/BF01978608pubmed: 7398848google scholar: lookup
        34. Martin MF, Dowd PM, Ring EF, Cooke ED, Dieppe PA, Kirby JD. Prostaglandin E1 infusions for vascular insufficiency in progressive systemic sclerosis. Ann Rheum Dis 1981 Aug;40(4):350-4.
          doi: 10.1136/ard.40.4.350pubmed: 7259326google scholar: lookup
        35. Baron M, Skrinskas G, Urowitz MB, Madras PN. Prostaglandin E1 therapy for digital ulcers in scleroderma. Can Med Assoc J 1982 Jan 1;126(1):42-5.
          pubmed: 7199370
        36. Moncada S. Eighth Gaddum Memorial Lecture. University of London Institute of Education, December 1980. Biological importance of prostacyclin. Br J Pharmacol 1982 May;76(1):3-31.
          doi: 10.1111/j.1476-5381.1982.tb09186.xpubmed: 7044460google scholar: lookup
        37. El Tahir KE, Williams KI. Factors affecting prostacyclin formation by the rat pregnant myometrium. Br J Pharmacol 1980;71(2):641-9.
          doi: 10.1111/j.1476-5381.1980.tb10985.xpubmed: 7008888google scholar: lookup
        38. Simmet T, Förstermann U, Peskar BA. Effect of exogenous and endogenous prostacyclin on the contractility of rabbit splenic capsular smooth muscle. Naunyn Schmiedebergs Arch Pharmacol 1980 Jul;312(3):245-53.
          doi: 10.1007/BF00499154pubmed: 6995863google scholar: lookup
        39. Smith JB. The prostanoids in hemostasis and thrombosis: a review. Am J Pathol 1980 Jun;99(3):743-804.
          pubmed: 6992594
        40. Kikawa Y, Narumiya S, Fukushima M, Wakatsuka H, Hayaishi O. 9-Deoxy-delta 9, delta 12-13,14-dihydroprostaglandin D2, a metabolite of prostaglandin D2 formed in human plasma. Proc Natl Acad Sci U S A 1984 Mar;81(5):1317-21.
          doi: 10.1073/pnas.81.5.1317pubmed: 6584883google scholar: lookup
        41. Kent RS, Diedrich SL, Whorton AR. Regulation of vascular prostaglandin synthesis by metabolites of arachidonic acid in perfused rabbit aorta. J Clin Invest 1983 Aug;72(2):455-65.
          doi: 10.1172/jci110993pubmed: 6409932google scholar: lookup
        42. Blair IA, MacDermot J. The binding of [3H]-prostacyclin to membranes of a neuronal somatic hybrid. Br J Pharmacol 1981 Mar;72(3):435-41.
          doi: 10.1111/j.1476-5381.1981.tb10994.xpubmed: 6266565google scholar: lookup
        43. O'Grady J, Hedges A, Whittle BJ, Al-Sinawi LA, Mekki QA, Burke C, Moody SG, Moti MJ, Hassan S. A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. Br J Clin Pharmacol 1984 Dec;18(6):921-33.
          doi: 10.1111/j.1365-2125.1984.tb02565.xpubmed: 6085004google scholar: lookup
        44. Hawkins SJ, Black CM, Hall ND, McGregor A, Ring EF, Maddison PJ. Clinical and laboratory effects of nifedipine in Raynaud's phenomenon. Rheumatol Int 1986;6(2):85-8.
          doi: 10.1007/BF00541510pubmed: 3764307google scholar: lookup
        45. Tachibana M, Fex J, Urade Y, Hayaishi O. Brain-type prostaglandin D synthetase occurs in the rat cochlea. Proc Natl Acad Sci U S A 1987 Nov;84(21):7677-80.
          doi: 10.1073/pnas.84.21.7677pubmed: 3118375google scholar: lookup
        46. Hamid-Bloomfield S, Whittle BJ. Prostaglandin D2 interacts at thromboxane receptor-sites on guinea-pig platelets. Br J Pharmacol 1986 Aug;88(4):931-6.
          doi: 10.1111/j.1476-5381.1986.tb16268.xpubmed: 3017497google scholar: lookup
        47. Narumiya S, Toda N. Different responsiveness of prostaglandin D2-sensitive systems to prostaglandin D2 and its analogues. Br J Pharmacol 1985 Jun;85(2):367-75.
          doi: 10.1111/j.1476-5381.1985.tb08870.xpubmed: 2992661google scholar: lookup
        48. Hamid S, Whittle BJ. Interaction of prostaglandin D2 with prostacyclin, carbacyclin and the hydantoin prostaglandin, BW245C, in guinea-pig platelets. Br J Pharmacol 1985 May;85(1):285-90.
          doi: 10.1111/j.1476-5381.1985.tb08858.xpubmed: 2992652google scholar: lookup
        49. Vanderwel M, Haslam RJ. Inhibition and subsequent enhancement of platelet responsiveness by prostacyclin in the rabbit. Relationship to platelet adenosine 3',5'-cyclic monophosphate. J Clin Invest 1985 Jul;76(1):233-40.
          doi: 10.1172/JCI111952pubmed: 2991338google scholar: lookup
        50. Hamid-Bloomfield S, Whittle BJ. Antagonism of PGD2 vasodepressor responses in the rat in vivo by the novel, selective antagonist, BW A868C. Br J Pharmacol 1989 Feb;96(2):307-12.
          doi: 10.1111/j.1476-5381.1989.tb11818.xpubmed: 2647205google scholar: lookup
        51. Ikai K, Ujihara M, Urade Y. Changes of the activities of enzymes involved in prostaglandin synthesis in rat skin during development and aging. Arch Dermatol Res 1989;281(6):433-6.
          doi: 10.1007/BF00455331pubmed: 2512861google scholar: lookup
        52. Trist DG, Collins BA, Wood J, Kelly MG, Robertson AD. The antagonism by BW A868C of PGD2 and BW245C activation of human platelet adenylate cyclase. Br J Pharmacol 1989 Feb;96(2):301-6.
          doi: 10.1111/j.1476-5381.1989.tb11817.xpubmed: 2466517google scholar: lookup
        53. Keery RJ, Lumley P. AH6809, a prostaglandin DP-receptor blocking drug on human platelets. Br J Pharmacol 1988 Jul;94(3):745-54.
          doi: 10.1111/j.1476-5381.1988.tb11584.xpubmed: 2460179google scholar: lookup
        54. Mizumura K, Sato J, Kumazawa T. Comparison of the effects of prostaglandins E2 and I2 on testicular nociceptor activities studied in vitro. Naunyn Schmiedebergs Arch Pharmacol 1991 Sep;344(3):368-76.
          doi: 10.1007/BF00183013pubmed: 1961261google scholar: lookup
        55. Gray SJ, Giles H, Posner J. The effect of a prostaglandin DP-receptor partial agonist (192C86) on platelet aggregation and the cardiovascular system in healthy volunteers. Br J Clin Pharmacol 1992 Oct;34(4):344-51.
          doi: 10.1111/j.1365-2125.1992.tb05641.xpubmed: 1457268google scholar: lookup
        56. Simon B, Kather H. Prostaglandins and the human mucosal alimentary cyclic AMP system. Dig Dis Sci 1979 Dec;24(12):970.
          doi: 10.1007/BF01311957pubmed: 228916google scholar: lookup
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