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Thromb Haemost 1977; 38(04): 1030-1041
DOI: 10.1055/s-0038-1651921
Original Article
Schattauer GmbH

Prostaglandin Endoperoxide – Thromboxane Synthesis and Dense Granule Secretion as Positive Feedback Loops in the Propagation of Platelet Responses during “The Basic Platelet Reaction”

Holm Holmsen
1   Specialized Center for Thrombosis Research, Temple University Health Science Center, Philadelphia, Pa. 19140, U.S.A.
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Publication Date:
04 July 2018 (online)

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Summary

Platelets respond to a great variety of stimuli by a sequential display of shape change, aggregation, prostaglandin/thromboxane synthesis – dense granule secretion and α-granule secretion. It is suggested that these responses are independent of each other, and caused by an increase in the concentration of a second messenger, liberated to the cytoplasm through the interaction between an extracellular agonist and the platelet membrane. The extent of the propagation of responses is determined by the strength of the stimulus. Stimuli can be subdivided into 1) original, applied stimuli and 2) platelet-produced stimuli (substances secreted from dense granules, prostaglandins and thromboxanes); these stimuli may act synergistically. In this way the platelet has two apparently independent means of potentiating their response to external stimuli which act as two separate positive feedback loops.

 

  • References

  • 1 Baumgartner H. R, Born G. V. R. 1968; Effects of 5-hydroxytryptamine on platelet aggregation. Nature 218: 137.
    CrossrefPubMedSearch in Google Scholar
  • 2 Bills T. K, Smith J. B, Silver M. J. 1976; Metabolism of [14C] arachidonic acid by human platelets. Biochimica et Biophysica Acta 424: 303.
    CrossrefPubMedSearch in Google Scholar
  • 3 Born G. V. R. 1970; Observations on the change in shape of blood platelets brought about by adenosine diphosphate. Journal of Physiology 209: 487.
    CrossrefPubMedSearch in Google Scholar
  • 4 Charo I. F, Feinman R. D, Detwiler T. C. 1976; Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochemical and Biophysical Research Communications 72: 1462.
    CrossrefPubMedSearch in Google Scholar
  • 5 Charo I. F, Feinman D, Detwiler T. C, Smith J. B, Ingerman C. M, Silver M. J. 1977; Independent induction of platelet aggregation and secretion by prostaglandin endoperoxides and thromboxane A2-like material. Nature 265: 66.
    CrossrefPubMedSearch in Google Scholar
  • 6 Derksen A, Cohen P. 1975; Patterns of fatty acid release from endogenous substrates by human platelet homogenates and membranes. Journal of Biological Chemistry 250: 9342.
    PubMedSearch in Google Scholar
  • 7 Daniel J. L, Holmsen H, Adelstein R. S. 1977; Thrombin-stimulated myosin phosphorylation in intact platelets and its possible involvement in secretion. Thrombosis and Haemostasis 38: 984.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 T. C. (1977): Personal Communication.
    PubMed
  • 9 Feinman R. D, Detwiler T. C. 1974; Platelet secretion induced by divalent cation ionophores. Nature 249: 172.
    CrossrefPubMedSearch in Google Scholar
  • 10 Feinman R. D, Azbinski M. P, Lubowsky J. 1977. Simultaneous measurement of aggregation and secretion. In: Platelet Function Testing. (eds.) Day H. J, Holmsen H, Zucker M. B. US Government Printing Office; (DHEW-Pub-NIH-77-108), in press.
    Search in Google Scholar
  • 11 Feinstein M. B, Giekers K. J, Fraser F. B. 1975; An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. Journal of Pharmacology and Experimental Therapeutics 197: 215.
    PubMedSearch in Google Scholar
  • 12 Fukami M. H, Holmsen H, Bauer J. 1976; Thrombin-induced oxygen consumption, malondialdehyde formation and serotonin secretion in human platelets. Biochimica et Biophysica Acta 428: 253.
    CrossrefPubMedSearch in Google Scholar
  • 13 Fukami M. H, Salganicoff L. 1977; Human platelet storage organelles. Thrombosis and Haemostasis 38: 963.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Gerrard J. M, Peterson D, Townsend D, White J. G. 1976 Prostaglandins and platelet contraction. Circulation. 54. Abstract #767.
    PubMedSearch in Google Scholar
  • 15 Hamberg M, Svensson J, Samuelsson B. 1975; Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proceedings of the National Academy of Sciences of the United States of America 72: 2994.
    CrossrefPubMedSearch in Google Scholar
  • 16 Haslam R. J, Lynham J. A. 1976; Increased phosphorylation of specific blood platelet proteins in association with the release reaction. Biochemical Society Transactions 4: 694.
    CrossrefPubMedSearch in Google Scholar
  • 17 Holme S, Holmsen H. 1975; ADP-induced refractory state of platelets in vitro. I. Methodological studies on aggregation in platelet-rich plasma. Scandinavian Journal of Haematology 15: 96.
    PubMedSearch in Google Scholar
  • 18 Holme S, Sixma J. J, Wester J, Holmsen H. 1977; ADP-induced refreactory state of platelets in vitro II. Functional and ultra studies on gel filtered platelets. Scandinavian Journal of Haematology 18: 267.
    PubMedSearch in Google Scholar
  • 19 Holmsen H. 1972; The platelet: its membrane, biochemistry and physiology. Clinics in Haematology 1: 235.
    PubMedSearch in Google Scholar
  • 20 Holmsen H. 1974. Are platelet shape change, aggregation and release reaction tangible manifestations of one basic platelet function?. In: Baldini M. G, Ebbe S. (eds.) Platelets: Production Function Transfusion and Storage. Grune and Stratton; New York: 207.
    Search in Google Scholar
  • 21 Holmsen H, Setkowsky C. A, Day H. J. 1974; Effects of antimycin and 2-deoxyglucose on adenine nucleotides in human platelets. The role of metabolic ATP levels in primary aggregation, secondary aggregation and shape change of human platelets. Biochemical Journal 144: 385.
    CrossrefPubMedSearch in Google Scholar
  • 22 Holmsen H. 1975. Biochemistry of the platelet release reaction. In: Biochemistry and Pharmacology of Blood Platelets. CIBA Foundation Symposium, No. 35. Elsevier; Amsterdam: 175.
    Search in Google Scholar
  • 23 Holmsen H. 1976; Classification and possible mechanisms of action of some drugs that inhibit platelet aggregation. Series Haematologica 8: 50.
    PubMedSearch in Google Scholar
  • 24 Holmsen H. 1977. Platelet energy metabolism in relation to function. In: Mills D. C B, Pareti F. I. (eds.) Platelets and Thrombosis. Acad. Press; New York: in press.
    Search in Google Scholar
  • 25 Holmsen H. and Dangelmaier C. A. (1977): Unpublished observations.
    PubMed
  • 26 Holmsen H. and Robkin L. (1977): Unpublished observations.
    PubMed
  • 27 Holmsen H, Setkowsky-Dangelmaier C. A. 1977; Adenine nucleotide metabolism of blood platelets. X. Formaldehyde stops centrifugation induced secretion after A 23187-stimulation and causes breakdown of metabolic ATP. Biochimica et Biophysica Acta 497: 46.
    CrossrefPubMedSearch in Google Scholar
  • 28 Kinlough-Rathbone R. L, Chahil A, Packham M. A, Reimers H.-J, Mustard J. F. 1975; Effect of ionophore A 23 187 on thrombin-degranulated washed rabbit platelets. Thrombosis Research 7: 435.
    CrossrefPubMedSearch in Google Scholar
  • 29 Kinlough-Rathbone R. L, Reimers H. J, Mustard J. F. 1976; Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction. Science 192: 1011.
    CrossrefPubMedSearch in Google Scholar
  • 30 Lages B. A, Weiss H. J. 1977; Platelet aggregation and secretion: Effects of anticoagulants and divalent cation chelators. (Abstract). Thrombosis and Haemostasis 38: 123.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Malmsten C, Hamberg M, Svensson J, Samuelsson B. 1975; Physiological role of an endoperoxide in human platelets: Hemostatic defect due to platelet cyclooxygenase deficiency. Proceedings of the National Academy of Sciences of the United States of America 72: 1446.
    CrossrefPubMedSearch in Google Scholar
  • 32 Mills D. C. B, Roberts G. C. K. 1967; Membrane active drugs and the aggregation of human blood platelets. Nature 213: 5071.
    PubMedSearch in Google Scholar
  • 33 Mustard J. F, Perry D. W, Kinlough-Rathbone R. L, Packham M. A. 1975; Factors responsible of ADP-induced release reaction of human platelets. American Journal of Physiology 228: 1757.
    PubMedSearch in Google Scholar
  • 34 Niewiarowski S, Thomas D. P. 1966; Platelet aggregation by ADP and thrombin. Nature 212: 1344.
    PubMedSearch in Google Scholar
  • 35 O’Brien J. R. 1964; A comparison of platelet aggregation produced by seven compounds and a comparison of their inhibitors. Journal of Clinical Pathology 17: 275.
    CrossrefPubMedSearch in Google Scholar
  • 36 Packham M. A, Guccione M. A, Chang P. L, Mustard J. F. 1975; Platelet aggregation and release: effects of low concentration of thrombin or collagen. American Journal of Physiology 225: 38.
    PubMedSearch in Google Scholar
  • 37 Ritchie J. M, Cohen P. J. 1975. Cocaine, procaine and other synthetic local anesthetics. In: Goodman L. S, Gilman A. (eds.) The pharmacological basis of therapeutics. Macmillan; New York: 379-386.
    Search in Google Scholar
  • 38 Rittenhouse-Simmons S, Russell F. A, Deykin D. 1976; Transfer of arachidonic add to human platelet plasmalogen in response to thrombin. Biochemical and Biophysical Research Communications 70: 295.
    CrossrefPubMedSearch in Google Scholar
  • 39 Ross R, Glomset J, Kariya B, Harker L. 1974; A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cell in vitro. Proceedings of the National Academy of Sciences of the United States of America 71: 1207.
    CrossrefPubMedSearch in Google Scholar
  • 40 Silver M. J, Smith J. B, Ingerman C, Kocsis J. J. 1973; Arachidonic acid-induced human platelet aggregation and prostaglandin formation. Prostaglandin 4: 863.
    PubMedSearch in Google Scholar
  • 41 Smith J. B, Ingerman C, Kocsis J. J, Silver M. J. 1973; Formation of prostaglandins during the aggregation of human blood platelets. Journal of Clinical Investigation 52: 965.
    CrossrefPubMedSearch in Google Scholar
  • 42 Smith J. B, Ingerman C. M, Silver M. J. 1976; Malondialdehyde formation as an indicator of prostaglandin production by human platelets. Journal of Laboratory and Clinical Medicine 88: 167.
    PubMedSearch in Google Scholar
  • 43 Smith J. B, Sedar A. W, Ingerman C. M, Silver M. J. 1977. Prostaglandin ednoperoxides: Platelet shape change, aggregation and the release reaction. In: Mills D. C. B. Pareti. (eds.) Platelets and Thrombosis. Acad. Press; New York: in press.
    Search in Google Scholar
  • 44 Taylor Jr F. B, Müller-Eberhard H. J. 1970; Qualitative description of factors involved in the retraction and lysis of dilute whole blood clots and in the aggregation and retraction of platelets. The Journal of Clinical Investigation 49: 2068.
    CrossrefPubMedSearch in Google Scholar
  • 45 Thomas D. P. 1968. The role of platelet catecholamines in the aggregation of platelets by collagen and thrombin. In: Hagen E, Wechsler W, Zillken F. (eds.) Experimental Biology and Medicine. S. Karger; New York: 129.
    Search in Google Scholar
  • 46 Walsh P. N, Mills D. C. B, White J. G. 1977; Metabolism and function of human platelets washed by albumin density gradient separation. British Journal of Haematology 36: 285.
    PubMedSearch in Google Scholar
  • 47 Weiss H. J, Willis A. L, Kuhn D, Brand H. 1976; Prostaglandin E2 potentiation of platelet aggregation induced by Lass endoperoxide: absent in storage pool disease, normal after aspirin ingestion. British Journal of Haematology 32: 257.
    CrossrefPubMedSearch in Google Scholar
  • 48 White J. G. 1969; The dense bodies of human platelets: Inherent electron opacity of the serotonin storage particles. Blood 33: 598.
    PubMedSearch in Google Scholar
  • 49 White J. G. 1972; Interaction of membrane systems in blood platelets. American Journal of Pathology 66: 295.
    PubMedSearch in Google Scholar
  • 50 White J. G. 1973; Shape Change. Thrombosis et Diathesis Haemorrhagica Suppl. 60: 159-171.
    PubMedSearch in Google Scholar
  • 51 Zucker-Franklin D, Nachman R. L, Marcus A. J. 1967; Ultrastructure of thrombosthenin, the contractile protein of human blood platelets. Science 157: 945.
    CrossrefPubMedSearch in Google Scholar