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Bioassay of Prostacyclin and Thromboxane A2

  • Ryszard J. Gryglewski
Part of the NATO Advanced Study Institutes Series book series

Abstract

Bioassay of the products of cyclo-oxygenation of arachidonic acid (AA) is not only a laboratory technique, it is also a way of biological thinking. Unlike phychicochemical techniques bioassay offers a continuous monitoring of changes in concentration of prostaglandins (PGs), prostacyclin (PGI2) and thromboxane A2 (TXA2) in blood of anesthetized animals or in the perfusate from isolated organs. The price which is paid for the devotion to bioassay is uncertainty about the real chemical nature of a substance which is assayed. The approximation is sometimes very near to the certainty but it never reaches this point. Therefore, we frequently refer to PGI2-like or TXA2-like substances instead of the firm statement — this is PGI2 and that is TXA2. However, this handicap may appear as an advantage of bioassay. A rabbit aorta contracting substance (RCS) had been described as an unstable metabolite of AA before cyclic endoperoxides (PGG2 and PGH2) and TXA2 were discovered. The existence of PGI2 was discovered only because of its “peculiar” behaviour in the bioassay system. Bioassay, when mastered, stimulates research because of its yet unexploited possibilities. Bioassay was created by pharmacologists and thus a number of pharmacological “tricks” are available to increase its specifity and sensitivity.

Keywords

Platelet Rich Plasma Thromboxane Synthetase Collagen Strip Thromboxane Synthetase Inhibitor Platelet Clump 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    R. J. Gryglewski, S. Buntin S. Moncada, R. J. Flower and J. R. Vane, Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685 (1976).PubMedGoogle Scholar
  2. 2.
    S. Moncada, R. J. Gryglewski, S. Bunting and J. R. Vane, An enzyme isolated from arteries transform prostaglandin endoperoxides to an unstable substance than inhibits platelet aggregation. Nature, 263: 663 (1976).PubMedCrossRefGoogle Scholar
  3. 3.
    C. Omini, S. Moncada and J. R. Vane, The effects of prostacyclin (PGI2) on tissues which detect prostaglandins (PGs). Prostaglandins, 14: 625 (1977).PubMedGoogle Scholar
  4. 4.
    G. J. Dusting, S. Moncada and J. R. Vane, Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachidonic acid. Prostaglandins, 13: 3 (1977).PubMedGoogle Scholar
  5. 5.
    S. Moncada, K. G. Mugridge and B. J. R. Whittle, The differential response of a novel bioassay tissue, the rabbit transverse stomach-strip to prostacyclin (PGI2) and other prostaglandins. Brit. J. Pharmacol., 61: 451P (1977).Google Scholar
  6. 6.
    J. R. Vane, The use of isolated organs for detection of active substances in circulating blood. Brit. J. Pharmacol. 23: 360 (1964).PubMedGoogle Scholar
  7. 7.
    R. J. Gryglewski-and K. C. Nicolaou, A triple test for screening biological activity of prostacyclin analogues. Experientia, 34: 1336 (1978).CrossRefGoogle Scholar
  8. 8.
    R. J. Gryglewski, R. Korbut and J. Splawinski, Endogenous mechanisms which regulate prostacyclin release. Washington Conference on Prostaglandins, 29 May - 3 June 1979, in press.Google Scholar
  9. 9.
    R. J. Gryglewski, R. Korbut, A. Ocetkiewicz and J. Stachura, In vivo method for quantitation of anti-platelet potency of drugs. Naunyn-Schmiedeberg’s Arch. Pharmacol., 302:25 (1978).Google Scholar
  10. 10.
    R. J. Gryglewski, R. Korbut, A. Ocetkiewicz, J. Splawinski, B. Wojtaszek and J. Swiens, Lungs as generator or prostacyclinhypothesis on physiological significance. Naunyn-Schmiedeberg’s Arch. Pharmacol., 304: 45 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    R. J. Gryglewski, R. Korbut and A. Ocetkiewicz, Generation of prostacyclin by lungs in vivo and its release into the arterial blood. Nature, 273: 765 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    R. J. Gryglewski, R. Korbut and A. Ocetkiewicz, Reversal of platelet aggregation by prostacyclin. Pharmacol. Res. Commun., 10: 185 (1978).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Moncada, R. Korbut and J. R. Vane, Prostacyclin is a circulating hormone. Nature, 273: 767 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    R. J. Gryglewski, A. Szczeklik and R. Nizankowski, Anti-platelet action of intravenous infusion of prostacyclin in man. Thromb. Res., 13: 153 (1978).PubMedCrossRefGoogle Scholar
  15. 15.
    B. J. R. Whittle, S. Moncada and J. R. Vane, Comparison of the effects of prostacyclin (PGI2), prostaglandins El and D2 on platelet aggregation in different species. Prostaglandins, 16: 373 (1978).PubMedGoogle Scholar
  16. 16.
    A. Szczeklik and R. J. Gryglewski, Thromboxane A2 synthesis by platelets of patients with coronary heart disease. In: “International Conference on Atherosclerosis”. L. A. Carlson, R. Paoletti, C. R. Sirtori and G. Weber, eds. (Raven Press, New York, (1978)).Google Scholar
  17. 17.
    E. Marcinkiewicz, L. Grodzinska and R. J. Gryglewski, Platelet aggregation and thromboxane A2 formation in cat platelet rich plasma. Pharmacol. Res. Commun., 10: 1 (1978).PubMedCrossRefGoogle Scholar
  18. 18.
    P. Needleman, S. Moncada, S. Bunting, J. R. Vane, M. Ramberg and B. Samuelsson, Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature, 261: 558 (1976).PubMedCrossRefGoogle Scholar
  19. 19.
    R. J. Gryglewski, A. Zmuda, R. Korbut, E. Krecioch and K. Bieron, Selective inhibition of thromboxane A2 biosynthesis in blood platelets. Nature, 267: 627 (1977).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Ryszard J. Gryglewski
    • 1
  1. 1.Department of PharmacologyCopernicus Academy of MedicineGrzegorzeckaPoland

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