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. 1978 May;63(1):35–42. doi: 10.1111/j.1476-5381.1978.tb07771.x

Role of platelets in aspirin-sensitive bronchoconstriction in the guinea-pig; interactions with salicylic acid

Jean Lefort, Bernardo B Vargaftig
PMCID: PMC1668291  PMID: 647162

Abstract

1 The bronchoconstriction caused in the guinea-pig by arachidonic acid (AA), bradykinin, adenosine diphosphate (ADP) and adenosine triphosphate (ATP) was correlated with effects on platelets. ATP and ADP produced a brief thrombocytopenia and AA a more prolonged one. Bradykinin had no effect on platelets.

2 Aspirin inhibited bronchoconstriction and thrombocytopenia produced by AA and part of the bronchoconstriction produced by ATP, but had no effect against ADP. Thrombocytopenia produced by ADP and ATP was not affected by aspirin or indomethacin.

3 Platelet depletion by antiserum prevented bronchoconstriction in response to ADP and to ATP, but not in response to bradykinin or to AA, showing that platelets are not involved in aspirin-sensitive bronchoconstriction. Infusions of ADP reduced bronchoconstriction and thrombocytopenia in response to ADP itself and to ATP, but not to AA. Bronchoconstriction by ADP or ATP involves an action on platelets. Only that due to ATP is partially dependent on the activity of prostaglandin synthetase.

4 ATP induced aggregation in vitro in guinea-pig platelet-rich plasma (PRP). Rabbit PRP responded only when ATP was first incubated with guinea-pig plasma. The aggregating compound formed was probably ADP, since it was destroyed by apyrase. Its formation was not inhibited by aspirin or indomethacin, indicating that aspirin inhibits ATP-induced bronchoconstriction by a different mechanism.

5 The aggregating effect of ATP on guinea-pig platelets was inhibited by concentrations of apyrase that block ADP-induced aggregation, and potentiated by lower concentrations of apyrase.

6 Adenosine 5′-tetraphosphate did not aggregate platelets in vivo or in vitro. In vitro aggregation occurred when apyrase was added, suggesting transformation into ADP. Adenosine 5′-tetraphosphate and apyrase inhibited aggregation due to ADP, but failed to affect that due to AA. This suggests that aggregation involving products of prostaglandin synthesis does not require ADP.

7 Salicylic acid did not interfere with bronchoconstriction or aggregation due to AA, but prevented inhibition by aspirin when the weight ratio, salicylic acid:aspirin was 4:1. Salicyclic acid may be useful in studies of potential inhibitors of thromboxane A2 synthesis and of thromboxane A2-dependent processes in vivo and in vitro.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  2. Bunting S., Moncada S., Vane J. R. The effects of prostagladin endoperoxides and thromboxane A2 on strips of rabbit coeliac artery and certain other smooth muscle preparations [proceedings]. Br J Pharmacol. 1976 Jul;57(3):462P–463P. [PMC free article] [PubMed] [Google Scholar]
  3. Collier H. O. New light on how aspirin works. Nature. 1969 Jul 5;223(5201):35–37. doi: 10.1038/223035a0. [DOI] [PubMed] [Google Scholar]
  4. Daly M. J. Pulmonary mechanical effects of experimental lung embolism and their modification by bronchodilator drugs in the guinea-pig. Br J Pharmacol. 1974 Aug;51(4):599–601. doi: 10.1111/j.1476-5381.1974.tb09679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ezer E., Palosi E., Hajós G., Szporny L. Antagonism of the gastrointestinal ulcerogenic effect of some nonsteroidal anti-inflammatory agents by sodium salicylate. J Pharm Pharmacol. 1976 Aug;28(8):655–656. doi: 10.1111/j.2042-7158.1976.tb02824.x. [DOI] [PubMed] [Google Scholar]
  6. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harrison M. J., Brossmer R. Inhibition of ADP-induced platelet aggregation by adenosine tetraphosphate. Thromb Haemost. 1976 Nov 30;36(2):388–391. [PubMed] [Google Scholar]
  9. MOLNAR J., LORAND L. Studies on apyrases. Arch Biochem Biophys. 1961 May;93:353–363. doi: 10.1016/0003-9861(61)90278-8. [DOI] [PubMed] [Google Scholar]
  10. Pinckard R. N., Hawkins D., Farr R. S. The inhibitory effect of salicylate on the acetylation of human albumin by acetylsalicylic acid. Arthritis Rheum. 1970 Jul-Aug;13(4):361–368. doi: 10.1002/art.1780130401. [DOI] [PubMed] [Google Scholar]
  11. Piper P. J., Vane J. R. Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature. 1969 Jul 5;223(5201):29–35. doi: 10.1038/223029a0. [DOI] [PubMed] [Google Scholar]
  12. Rosenberg F. J., Gimber-Phillips P. E., Groblewski G. E., Davison C., Phillips D. K., Goralnick S. J., Cahill E. D. Acetylsalicylic acid: inhibition of platelet aggregation in the rabbit. J Pharmacol Exp Ther. 1971 Nov;179(2):410–418. [PubMed] [Google Scholar]
  13. Roth G. J., Stanford N., Majerus P. W. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073–3076. doi: 10.1073/pnas.72.8.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ts'ao C. Rat platelet aggregation by ATP. Aggregometrical and ultrastructural comparison with aggregations induced by ADP and collagen. Am J Pathol. 1976 Dec;85(3):581–594. [PMC free article] [PubMed] [Google Scholar]
  15. VANE J. R. THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD. Br J Pharmacol Chemother. 1964 Oct;23:360–373. doi: 10.1111/j.1476-5381.1964.tb01592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Van Arman C. G., Nuss G. W., Risley E. A. Interactions of aspirin, indomethacin and other drugs in adjuvant-induced arthritis in the rat. J Pharmacol Exp Ther. 1973 Nov;187(2):400–414. [PubMed] [Google Scholar]
  17. Vargaftig B. B. Carrageenan and thrombin trigger prostaglandin synthetase-independent aggregation of rabbit platelets: inhibition by phospholipase A2 inhibitors. J Pharm Pharmacol. 1977 Apr;29(4):222–228. doi: 10.1111/j.2042-7158.1977.tb11293.x. [DOI] [PubMed] [Google Scholar]
  18. Vargaftig B. B., Coignet J. L., de Vos C. J., Grijsen H., Bonta I. L. Mianserin hydrochloride: peripheral and central effects in relation to antagonism against 5-hydroxytryptamine and tryptamine. Eur J Pharmacol. 1971 Nov-Dec;16(3):336–346. doi: 10.1016/0014-2999(71)90036-7. [DOI] [PubMed] [Google Scholar]
  19. Vargaftig B. B., Dao N. Release of vasoactive substances from guinea-pig lungs by slow-reacting substance c and arachidonic acid. Its blockade by nonsteroid anti-inflammatory agents. Pharmacology. 1971;6(2):99–108. doi: 10.1159/000136231. [DOI] [PubMed] [Google Scholar]
  20. Vargaftig B. B., Lefort J. Acute hypotension due to carrageenan, arachidonic acid and slow reacting substance C in the rabbit: role of platelets and nature of pharmacological antagonism. Eur J Pharmacol. 1977 May 15;43(2):125–141. doi: 10.1016/0014-2999(77)90125-x. [DOI] [PubMed] [Google Scholar]
  21. Vargaftig B. B., Tranier Y., Chignard M. Inhibition by sulfhydryl agents of arachidonic acid-induced platelet aggregation and release of potential inflammatory substances. Prostaglandins. 1974 Oct 25;8(2):133–156. doi: 10.1016/0090-6980(74)90076-8. [DOI] [PubMed] [Google Scholar]
  22. Vargaftig B. B., Zirinis P. Platelet aggregation induced by arachidonic acid is accompanied by release of potential inflammatory mediators distinct from PGE2 and PGF2. Nat New Biol. 1973 Jul 25;244(134):114–116. doi: 10.1038/newbio244114a0. [DOI] [PubMed] [Google Scholar]
  23. Willis A. L., Kuhn D. C. A new potential mediator of arterial thrombosis whose biosynthesis is inhibited by aspirin. Prostaglandins. 1973 Jul;4(1):127–130. doi: 10.1016/0090-6980(73)90062-2. [DOI] [PubMed] [Google Scholar]

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