Thromb Haemost 1979; 41(03): 475-490
DOI: 10.1055/s-0038-1646800
Original Articles
Schattauer GmbH Stuttgart

The Action Mechanism of the Purified Platelet Aggregation Principle of Trimeresurus mucrosquamatus Venom

Chaoho Ouyang
The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
,
Che-Ming Teng
The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
› Author Affiliations
Further Information

Publication History

Received 11 October 1977

Accepted 10 August 1978

Publication Date:
09 July 2018 (online)

Summary

The minimal concentration of the platelet aggregation principle (Platelet Aggregoserpen- tin, PAS) necessary to induce platelet aggregation was 10 ng/ml, about one-hundredth of that of the crude venom. PAS induced the release of platelet factors 3 and 4 from platelets, but the released platelet factor 3 was easily inactivated by the anti-phospholipid effect of PAS. Pretreatment of platelets with neuraminidase potentiated PAS-induced platelet aggregation. PAS-induced platelet aggregation was independent on released ADP; it could occur in the ADP-removing systems, such as apyrase or a combination of phosphoenolpyruvate and pyruvate kinase. However, PAS-induced platelet aggregation could be inhibited by adenine nucleotides and adenosine.

PAS-induced platelet aggregation was inhibited by some anti-inflammatory agents, antimalarial drugs, local anesthetics, antihistamine and smooth muscle relaxants. After deaggregation of PAS-treated platelets, thrombin and sodium arachidonate could further induce platelet aggregation, but ADP and second dose of PAS could not. It is concluded that PAS-induced platelet aggregation is due to prostaglandin synthesis. Recent literatures on the mechanism of platelet aggregation were surveyed and the actions of PAS were discussed.

 
  • References

  • 1 Aledort LM, Niemetz J. 1968; Dissociation of platelet aggregation from clot retraction, potassium loss, and adenosine triphosphatase activity. Proceedings of the Society for Experimental Biology and Medicine 128: 658
  • 2 Ardlie NG, Glew G, Schultz BG, Schwartz CJ. 1967; Inhibition and reversal of platelet aggregation by methylxanthines. Thrombosis et Diathesis Haemorrhagica 18: 670
  • 3 Ardlie NG, Perry DW, Packham MA, Mustard JF. 1971; Influence of apyrase on stability of suspensions of washed rabbit platelets. Proceedings of the Society for Experimental Biology and Medicine 136: 1021
  • 4 Biran H, Dvilansky A, Nathan I, Live A. 1974; Impairement of human platelet aggregation and serotonin release caused in vitro by Echis colorata venom. Thrombosis et Diathesis Haemorrhagica 30: 191
  • 5 Boffa MC, Boffa GA. 1974 Correlations between the enzymatic and factors active on blood coagulation and platelet aggregation from the venom of Vipera aspis. Biochimica et Biophysica Acta.
  • 6 Boffa MC, Delori P, Soulier JP. 1972; Anticoagulant factors from Viperidae venoms. Platelet phospholipid inhibitors. Thrombosis et Diathesis Haemorrhagica 28: 509
  • 7 Bond GH, Hudgins PM. 1976; Inhibition of ATPase activity in human red cell membranes by tetracaine. Biochemical Pharmacology 25: 267
  • 8 Born GV R, Cross MJ. 1963; The aggregation of blood platelet. Journal of Physiology 168: 178
  • 9 Bradlow BA, Marcus AJ. 1966; Action of snake venom phospholipase A on isolated platelet membranes. Proceedings of the Society for Experimental Biology and Medicine 123: 889
  • 10 Cohen P, Derksen A. 1969; Comparison of phospholipid and fatty acid composition of human erythrocytes and platelets. British Journal of Haematology 17: 359
  • 11 Condrea E, De Vries A, Mayer J. 1962; Action of snake venom phospholipase A on free and lipoprotein-bound phospholipids. Biochimica et Biophysica Acta 58: 389
  • 12 Davey MG, Lüscher EF. 1965; Action of some coagulant snake venoms upon blood platelets. Nature (London) 207: 1037
  • 13 Davey MG, Luscher EF. 1967; Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature (London) 216: 857
  • 14 Davis JW, Yue KT N, Phillips PE. 1972; The effect of neuraminidase on platelet aggregation induced by ADP, norepinephrine, collagen or serotonin. Thrombosis et Diathesis Haemorrhagica 28: 221
  • 15 Day HJ, Holmsen H, Zucker MB. 1975; Methods for separating platelets from blood and plasma. Thrombosis et Diathesis Haemorrhagica 33: 648
  • 16 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
  • 17 Didisheim P, Kazmier FJ, Fuster V. 1974; Platelet inhibition in the management of thrombosis. Thrombosis et Diathesis Haemorrhagica 32: 21
  • 18 Feinstein M, Fiekers J, Fraser C. 1976; An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. Journal of Pharmacology and Experimental Therapeutics 197: 215
  • 19 Flower RJ, Blackwell GJ. 1976; The importance of phospholipase A2 in prostaglandin biosynthesis. Biochemical Pharmacology 25: 285
  • 20 Greenberg J, Packham MA, Cazenave JP, Reimers HJ, Mustard JF. 1975; Effects on platelet function of removal of platelet sialic acid by neuraminidase. Laboratory Investigations 32: 476
  • 21 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
  • 22 Hamberg M, Svensson J, Wakabayashi T, Samuelsson B. 1974; a Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proceedings of the National Academy of Sciences 71: 345
  • 23 Hamberg M, Svensson J, Wakabayashi T, Samuelsson B. 1974; b Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proceedings of the National Academy of Sciences 71: 3400
  • 24 Hampton J. 1971; Trends in the development of antithrombotic agents. American Journal of Cardiology 27: 659
  • 25 Harbury CB, Hershagold JE, Schrier SL. 1972; Requirements for aggregation of washed human platelets suspended in buffered salt solutions. Thrombosis et Diathesis Haemorrhagica 28: 2
  • 26 Haslam RJ. 1964; Role of adenosine diphosphate in the aggregation of human blood platelets by thrombin and by fatty acids. Nature 202: 765
  • 27 Haslam RJ. 1973; Interactions of the pharmacological receptors of blood platelets with adenyl cyclase. Seminar Haematologica 6: 333
  • 28 Haslam RJ, Lynham JA. 1972; Activation and inhibition of blood platelet adenylate cyclase by adenosine or by 2-chloroadenosine. Life Science 11: 1143
  • 29 HIRSH J, GENT M, GENTON E. 1975; The current status of platelet suppressive drugs in the treatment of thrombosis. Thrombosis et Diathesis Haemorrhagica 33: 406
  • 30 Hovig T. 1963; Aggregation of rabbit blood platelets produced in vitro by “saline extract” of tendons. Thrombosis et Diathesis Haemorrhagica 9: 248
  • 31 Jesse RL, Cohen P. 1976; Arachidonic acid release from diacyl phosphatidylethanolamine by human platelet membranes. Biochemical Journal 158: 283
  • 32 Kazimierczak W, Peret M, Máslínski C. 1976; The action of local anesthetics on histamine release. Biochemical Pharmacology 25: 1747
  • 33 Kirschmann C, Aloof S, De Vries A. 1963; Action of lysolecithin on blood platelets. Thrombosis et Diathesis Haemorrhagica 9: 512
  • 34 Kirschmann C, Condrea E, Moau N. 1964; Action of snake venom on human platelet phospholipids. Archives of the International Pharmacodyn 150: 372
  • 35 Kolata GB. 1975; Thromboxanes: The power behind the prostaglandins. Science 190 770: 812
  • 36 Leone G, Boni P, Vinceti A. 1976; Platelet aggregation by thimerosal, role of ADP and SH groups. Thrombosis and Haemostasis 35: 249
  • 37 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
  • 38 Macmillan DC. 1966; Secondary clumping effect in human citrated platelet-rich plasma produced by ADP and adrenaline. Nature (London) 211: 140
  • 39 Markus HB, Ball EG. 1969; Inhibition of lypolytic process in rat diphose tissue by antimalarial drugs. Biochimica et Biophysica Acta 187: 486
  • 40 Markwardt F, Barthel W, Glusa E, Hoffmann A. 1966; N-S Archives of Experimental Pathology. Pharmacology 252: 297
  • 41 Markwardt F, Hoffmann A. 1970; Effects of papaverine derivatives on cyclic AMP phosphodiesterase of human platelets. Biochemical Pharmacology 19: 2519
  • 42 Marney SR. 1971; Platelet aggregation in heparinized plasma and citrated plasma. Relationship to ADP and inhibition by cobra factor. Journal of Immunology 106: 82
  • 43 Mcnicol GP, Mitchell JR A, Reuter H, Van De Loo J. 1970; Platelet in thrombosis, their clinical significance and the evaluation of potential drugs. Thrombosis et Diathesis Haemorrhagica 31: 379
  • 44 Meyer CJ, Van Breemen C, Casteels R. 1972; The action of Lanthanum and D600 on the calcium exchange in the smooth muscle cells of the guinea-pig taenia coli. Pflueeers Archives 337 333
  • 45 Michel H, Caen JP, Born GV R, Miller R, Auriac GA, Meyer P. 1976; Relation between the inhibition of aggregation and the concentration of c-AMP in human and rat platelets. British Journal of Haematology 33: 27
  • 46 Mustard JF, Perry DW, Ardlie NG, Packham MA. 1972; Preparation of suspensions of washed platelets from humans. British Journal of Haematology 22: 193
  • 47 Nye SW, Graham JB, Brinkhous KM. 1962; The partial thromboplastin time as a screening test for the detection of latent bleeders. American Journal of Medical Science 243: 279
  • 48 O’Brien JR. 1962; Platelet aggregation. II. Some results from a new method of study. Journal of Clinical Pathology 15: 452
  • 49 Ouyang C, Teng CM. 1977 Purification and characterization of the platelet aggregation principle of Trimeresurus mucrosquamatus venom. Submitted for publication in Biochimica et Biophysica Acta.
  • 50 Packham MA, Warrior ES, Glynn MF, Senyi AS, Mustard JF. 1967; Alternation of the response of platelet to surface stimuli by pyrazole compounds. Journal of Experimental Medicine 126: 171
  • 51 Patscheke H, Brossmer R. 1975; Concanavalin A-induced aggregation of human blood platelets. Ca++-dependent and Ca++-independent effects. Thrombosis et Diathesis Haemorrhagica 33: 354
  • 52 Praga CA, Pogliani EM. 1973; Effect of temperature on ADP-induced platelet aggregation. Thrombosis et Diathesis Haemorrhagica 29: 183
  • 53 Reimers HJ, Kinlough-Rathbone RL, Cazenave JP, Senyi AF, Hirsh J, Packham MA, Mustard JF. 1976; In vitro and in vivo functions of thrombin-treated platelets. Thrombosis et Diathesis Haemorrhagica 35: 151
  • 54 Roth GJ, Majerus PW. 1975; The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particular fraction protein. Journal of Clinical Investigation 56: 624
  • 55 Salzman EW, Levine L. 1971; Cyclic 3’,5’-adenosine monophosphate in human blood platelets. II. Effect of N6-2’-0-dibutyryl cyclic 3’,5’-adenosine monophosphate on platelet function. Journal of Clinical Investigation 50: 131
  • 56 Samuelsson B, Granström E, Green K, Hamberg M, Hammarström S. 1975; Annual Review of Biochemistry. 44: 669
  • 57 Saxon A, Kattlove HE. 1976; Platelet inhibition by sodium nitroprusside, a smooth muscle inhibitor. Blood 47. 951
  • 58 Shtacher G, Crowley HJ, Dolton C. 1976; Inhibition of platelet aggregation by papaverinelike drugs: evidence for a novel mechanism of action. Biochemical Pharmacology 25: 1045
  • 59 Simard-Duquesne N. 1973; Enhancement by ADP of thrombin-induced aggregation in ADP- refractory platelets. Thrombosis et Diathesis Haemorrhagica 29: 445
  • 60 Sket D, Gubensek F. 1976; Pharmacological study of phospholipase A from Vipera ammodytes venom. Toxicon 14: 393
  • 61 Strong PN, Goerke J, Oberg G, Kelly RB. 1976; P-Bungarotoxin, a pre-synaptic toxin with enzymatic activity. Proceedings of the National Academy of Sciences USA 73: 178
  • 62 Thomson D, Forbes CD, Prentice CR M. 1973; A comparison of the effects of antihistamines on platelet function. Thrombosis et Diathesis Haemorrhagica 30: 547
  • 63 Ungaro PC, Beck TM, Mccaa WM, Hershagold EJ. 1973; The in vivo and in vitro effect of antihistamines on platelet aggregation. Thrombosis et Diathesis Haemorrhagica 30: 597
  • 64 Vane JR. 1971; Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature (New Biology) 231: 232
  • 65 Vargaftic BB, Hai ND. 1972; Selective inhibition by mepacrine of the release of »rabbit aorta contracting substance« evoked by the administration of bradykinin. Journal of Pharmacy and Pharmacology 24: 159
  • 66 Verhaeghe RH, Shepherd JT. 1976; Effect of nitroprusside on smooth muscle and adrenergic nerve terminals in isolated blood vessels. Journal of Pharmacology Experimental Therapeutics 199: 269
  • 67 Warlow C, Corina A, Ogston D, Douglas AS. 1974; The relationship between platelet aggregation and time interval after venepuncture. Thrombosis and Diathesis Haemorrhagica 31: 133
  • 68 WEISS HJ. 1976; Antiplatelet drugs - A new pharmacologic approach to the prevention of thrombosis. American Heart Journal 92: 86
  • 69 Yue KT N, Davis JW, Aldridge EG. 1973; Effect of aspirin and benadryl on human platelet oxidative phosphorylation and aggregation. Thrombosis et Diathesis Haemorrhagica 30: 577
  • 70 Zucker MB, Peterson J. 1968; Inhibition of adenosine diphosphate induced secondary aggregation and other platelet functions by acetylsalicylic acid ingestion. Proceedings of the Society of Experimental Biology and Medicine 127: 547