Download PDF
Thromb Haemost 1979; 42(04): 1193-1206
DOI: 10.1055/s-0038-1657015
Original Article
Schattauer GmbH Stuttgart

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

Barbara Nunn
The Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, England
› Author Affiliations
Further Information

Publication History

Received 10 October 1978

Accepted 26 March 1979

Publication Date:
23 August 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

 

  • References

  • 1 Baumgartner HR, Born GV R. 1968; Effects of 5-hydroxytryptamine on platelet aggregation. Nature 218: 137
    CrossrefPubMedGoogle Scholar
  • 2 Beutler E, Baluda MC. 1964; Simplified determination of blood adenosine triphosphate (ATP) using the firefly system. Blood 23: 688
    PubMedGoogle Scholar
  • 3 Born GV R. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 921
    PubMedGoogle Scholar
  • 4 Brecher G, Cronkite EP. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365
    CrossrefPubMedGoogle Scholar
  • 5 Clayton S, Cross MJ. 1963; The aggregation of blood platelets by catecholamines and by thrombin. Journal of Physiology 169: 82 p
    PubMedGoogle Scholar
  • 6 Deykin D. 1974; Emerging concepts of platelet function. New England Journal of Medicine 290: 144
    CrossrefPubMedGoogle Scholar
  • 7 Geratz JD, Tidwell RR, Brinkhous KM, Mohammed SF, Dann O, Loewe H. 1978; Specific inhibition of platelet agglutination and aggregation by aromatic amidine compounds. Thrombosis and Haemostasis 39: 411
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Hamberg M, Svensson J, Wakabayashi T, Samuelsson B. 1974; Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proceedings of the National Academy of Sciences 71: 345
    CrossrefPubMedGoogle Scholar
  • 9 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 72: 2994
    CrossrefPubMedGoogle Scholar
  • 10 Haslam RJ. 1964; Role of adenosine diphosphate in the aggregation of human blood-platelets by thrombin and fatty acids. Nature 202: 765
    CrossrefPubMedGoogle Scholar
  • 11 Haslam RJ. 1967. Mechanisms of blood platelet aggregation. In Johnson SA, Seegers WH. (eds.) Physiology of Haemostasis and Thrombosis. Charles C. Thomas; Springfield: 111., p. 88
    Google Scholar
  • 12 Haslam RJ, Lynham JA. 1972; Activation and inhibition of blood platelet adenylate cyclase by adenosine or by 2-chloroadenosine. Life Sciences 11 Part II 1143
    CrossrefPubMedGoogle Scholar
  • 13 Holmsen H, Holmsen I, Bernhardsen A. 1966; Microdetermination of adenosine diphosphate and adenosine triphosphate in plasma with the firefly luciferase system. Analytical Biochemistry 17: 456
    CrossrefPubMedGoogle Scholar
  • 14 Holmsen H, Day HJ, Storm E. 1969; Adenine nucleotide metabolism of blood platelets VI. Subcellar localization of nucleotide pools with different functions in the platelet release reaction. Biochimica et Biophysica Acta 186: 254
    CrossrefPubMedGoogle Scholar
  • 15 Hovig T. 1963; a Aggregation of rabbit blood platelets produced in vitro by saline “extract” of tendons. Thrombosis et Diathesis Haemorrhagica 9: 248
    PubMedGoogle Scholar
  • 16 Hovig T. 1963; b Release of a platelet-aggregating substance (Adenosine diphosphate) from rabbit blood platelets induced by saline “extract” of tendons. Thrombosis et Diathesis Haemorrhagica 9: 264
    PubMedGoogle Scholar
  • 17 Hugues J. 1960; Accolement des plaquettes au collagène. Compte rendu des séances de la Société de biologie, Paris 154: 866
    PubMedGoogle Scholar
  • 18 Kalckar KM. 1944; Adenylpyrophosphatase and myokinase. Journal of Biological Chemistry 153
    PubMedGoogle Scholar
  • 19 Kattlove H, Gomez MH. 1975; Collagen-induced platelet aggregation: the role of adenine nucleotides and the release reaction. Thrombosis et Diathesis Haemorrhagica 34: 795
    PubMedGoogle Scholar
  • 20 Kinlough-Rathbone RL, Packham MA, Mustard JF. 1977; Synergism between platelet aggregating agents: the role of the arachidonate pathway. Thrombosis Research 11: 567
    CrossrefPubMedGoogle Scholar
  • 21 Kjaerheim Å, Hovig T. 1962; The ultrastructure of haemostatic blood platelet plugs in rabbit mesenterium. Thrombosis et Diathesis Haemorrhagica 7: 1
    PubMedGoogle Scholar
  • 22 MacFarlane DE, Mills DC B. 1975; The effects of ATP on platelets: Evidence against the central role of released ADP in primary aggregation. Blood 46: 309
    PubMedGoogle Scholar
  • 23 Macmillan DC. 1966; Secondary clumping effect in human citrated platelet-rich plasma produced by adenosine diphosphate and adrenaline. Nature 211: 140
    CrossrefPubMedGoogle Scholar
  • 24 Maguire MH, Michal F. 1968; Powerful new aggregator of blood platelets - 2- chloroadenosine-5’-diphosphate. Nature 217: 571
    CrossrefPubMedGoogle Scholar
  • 25 Massini P, LüScher EF. 1972; On the mechanism by which cell contact induces the release reaction of blood platelets; the effect of cationic polymers. Thrombosis et Diathesis Haemorrhagica 27: 121
    PubMedGoogle Scholar
  • 26 Mills DC B, Robb IA, Roberts GC K. 1968; The release of nucleotides, 5- hydroxytryptamine and enzymes from human blood platelets during aggregation. Journal of Physiology 195: 715
    CrossrefPubMedGoogle Scholar
  • 27 Movat HZ, Mustard JF, Taichmann NS, Uriuhara T. 1965; Platelet aggregation and release of ADP, serotonin and histamine associated with phagocytosis of antigen-antibody complexes. Proceedings of the Society for Experimental Biology and Medicine 120: 232
    PubMedGoogle Scholar
  • 28 Mustard JF, Packham MA. 1970; Factors influencing platelet function: adhesion, release, and aggregation. Pharmacological Reviews 22: 97
    PubMedGoogle Scholar
  • 29 Nunn B. 1972; The role of adenosine diphosphate (ADP) in collagen-induced platelet aggregation. British Journal of Pharmacology 46: 579 P
    PubMedGoogle Scholar
  • 30 O’Brien JR. 1964; A comparison of platelet aggregation produced by seven compounds and a comparison of their inhibitors. Journal of Clinical Pathology 17: 275
    CrossrefPubMedGoogle Scholar
  • 31 Packham MA, Ardlie NG, Mustard JF. 1969; Effect of adenine compounds on platelet aggregation. American Journal of Physiology 217: 1009
    PubMedGoogle Scholar
  • 32 Packham MA, Guccione MA, Perry DW, Kinlough-Rathbone RL, Mustard JF. 1972; AMP inhibition of reactions of ADP with washed platelets from humans and rabbits. American Journal of Physiology 223: 419
    PubMedGoogle Scholar
  • 33 Packham MA, Guccione MA, Chang P-L, Mustard JF. 1973; Platelet aggregation and release: effects of low concentrations of thrombin or collagen. American Journal of Physiology 225: 38
    PubMedGoogle Scholar
  • 34 Packham MA, Kinlough-Rathbone RL, Reimers H-J, Scott S, Mustard JF. 1977. Mechanisms of platelet aggregation independent of adenosine diphosphate. In Silver MJ, Smith JB, Kocsis JJ. (eds.) Prostaglandins in Hematology. Spectrum Publications, Inc; New York: p 247
    Google Scholar
  • 35 Rosenberg MC, Holmsen H. 1968; Adenine nucleotide metabolism of blood platelets IV. Platelet aggregation response to exogenous ATP and ADP. Biochimica et Biophysica Acta 157: 280
    CrossrefPubMedGoogle Scholar
  • 36 Salzman EW, Chambers DA, Neri LL. 1966; Possible mechanism of aggregation of blood platelets by adenosine diphosphate. Nature 210: 167
    CrossrefPubMedGoogle Scholar
  • 37 Silver MJ, Smith JB, Ingerman C, Kocsis JJ. 1973; Arachidonic acid-induced human platelet aggregation and prostaglandin formation. Prostaglandins 4: 863
    CrossrefPubMedGoogle Scholar
  • 38 Sinakos Z, Caen JP. 1967; Platelet aggregation in mammalians (human, rat, rabbit, guinea pig, horse, dog). A comparative study. Thrombosis et Diathesis Haemorrhagica 17: 99
    PubMedGoogle Scholar
  • 39 Spaet TH, Lejnieks I. 1969; A technique for estimation of platelet-collagen adhesion. Proceedings of the Society for Experimental Biology and Medicine 132: 1038
    PubMedGoogle Scholar
  • 40 Thomas DP, Niewiarowski S, Ream VJ. 1970; Release of adenine nucleotides and platelet factor 4 from platelets of man and four other species. Journal of Laboratory and Clinical Medicine 75: 607
    PubMedGoogle Scholar
  • 41 Willis AL, Kuhn DC. 1973; A new potential mediator of arterial thrombosis whose biosynthesis is inhibited by aspirin. Prostaglandins 4: 127
    CrossrefPubMedGoogle Scholar
  • 42 Zucker MB, Borrelli J. 1962; Platelet clumping produced by connective tissue suspensions and by collagen. Proceedings of the Society for Experimental Biology and Medicine 109: 779
    PubMedGoogle Scholar