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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Jan;87(1):109–115. doi: 10.1111/j.1476-5381.1986.tb10162.x

The roles of prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation in man and the rat.

H Emms, G P Lewis
PMCID: PMC1916885  PMID: 3082399

Abstract

The effects of aspirin, carboxyheptylimidazole (CHI) and creatine phosphate/creatine phosphokinase (CP/CPK) on platelet aggregation and thromboxane B2 (TxB2) formation induced by collagen have been examined in vitro. Platelets from two species, man and the rat, have been used. In man, aspirin and CHI abolished TxB2 production but only partially inhibited aggregation. CP/CPK partially inhibited aggregation and TxB2 formation. In the rat, aspirin and CHI abolished TxB2 formation but had no effect on aggregation. CP/CPK completely inhibited aggregation and partially inhibited TxB2 generation. In man, collagen-induced aggregation is largely dependent on ADP and to a lesser extent on arachidonate metabolites whereas, in the rat, ADP alone mediates aggregation induced by this agonist. The results with CP/CPK suggest that TxB2 formation is dependent either on the prior release of platelet ADP or on aggregation itself rather than being responsible for the aggregation response.

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Selected References

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

  1. Best L. C., Holland T. K., Jones P. B., Russell R. G. The interrelationship between thromboxane biosynthesis, aggregation and 5-hydroxytryptamine secretion in human platelets in vitro. Thromb Haemost. 1980 Feb 29;43(1):38–40. [PubMed] [Google Scholar]
  2. Butler K. D., Maguire E. D., Smith J. R., Turnbull A. A., Wallis R. B., White A. M. Prolongation of rat tail bleeding time caused by oral doses of a thromboxane synthetase inhibitor which have little effect on platelet aggregation. Thromb Haemost. 1982 Feb 26;47(1):46–49. [PubMed] [Google Scholar]
  3. Chignard M., Vargaftig B. Dog platelets fail to aggregate when they form aggregating substances upon stimulation with arachidonic acid. Eur J Pharmacol. 1976 Jul;38(1):7–18. doi: 10.1016/0014-2999(76)90195-3. [DOI] [PubMed] [Google Scholar]
  4. Emms H., Lewis G. P. The effect of synthetic ovarian hormones on an in vivo model of thrombosis in the rat. Br J Pharmacol. 1985 Jan;84(1):243–248. [PMC free article] [PubMed] [Google Scholar]
  5. HOVIG T. RELEASE OF A PLATELET-AGGREGATING SUBSTANCE (ADENOSINE DIPHOSPHATE) FROM RABBIT BLOOD PLATELETS INDUCED BY SALINE "EXTRACT" OF TENDONS. Thromb Diath Haemorrh. 1963 Jul 15;143:264–278. [PubMed] [Google Scholar]
  6. Hennam J. F., Johnson D. A., Newton J. R., Collins W. P. Radioimmunoassay of prostaglandin F-2-alpha in peripheral venous plasma from men and women. Prostaglandins. 1974 Mar 25;5(6):531–542. doi: 10.1016/s0090-6980(74)80028-6. [DOI] [PubMed] [Google Scholar]
  7. Jose P. J., Page D. A., Wolstenholme B. E., Williams T. J., Dumonde D. C. Bradykinin-stimulated prostaglandin E2 production by endothelial cells and its modulation by antiinflammatory compounds. Inflammation. 1981 Dec;5(4):363–378. doi: 10.1007/BF00911100. [DOI] [PubMed] [Google Scholar]
  8. Kinlough-Rathbone R. L., Cazenave J. P., Packham M. A., Mustard J. F. Effect of inhibitors of the arachidonate pathway on the release of granule contents from rabbit platelets adherent to collagen. Lab Invest. 1980 Jan;42(1):28–34. [PubMed] [Google Scholar]
  9. Kinlough-Rathbone R. L., Packham M. A., Reimers H. J., Cazenave J. P., Mustard J. F. Mechanisms of platelet shape change, aggregation, and release induced by collagen, thrombin, or A23,187. J Lab Clin Med. 1977 Oct;90(4):707–719. [PubMed] [Google Scholar]
  10. Krishnamurthi S., Westwick J., Kakkar V. V. Regulation of human platelet activation--analysis of cyclooxygenase and cyclic AMP-dependent pathways. Biochem Pharmacol. 1984 Oct 1;33(19):3025–3035. doi: 10.1016/0006-2952(84)90604-x. [DOI] [PubMed] [Google Scholar]
  11. Lewis G. P., Watts I. S. Prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation of rabbit platelets. Br J Pharmacol. 1982 Apr;75(4):623–631. doi: 10.1111/j.1476-5381.1982.tb09183.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Siess W., Roth P., Weber P. C. Stimulated platelet aggregation, thromboxane B2 formation and platelet sensitivity to prostacyclin - a critical evaluation. Thromb Haemost. 1981 Jun 30;45(3):204–207. [PubMed] [Google Scholar]
  13. Smith J. B., Ingerman C., Kocsis J. J., Silver M. J. Formation of an intermediate in prostaglandin biosynthesis and its association with the platelet release reaction. J Clin Invest. 1974 May;53(5):1468–1472. doi: 10.1172/JCI107695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Vincent J. E., Zijlstra F. J. Formation by phospholipase A2 of prostaglandins and thromboxane A2-like activity in the platelets of normal and essential fatty acid deficient rats. Comparison with effect on human and rabbit platelets. Prostaglandins. 1977;14(6):1043–1053. doi: 10.1016/0090-6980(77)90284-2. [DOI] [PubMed] [Google Scholar]
  15. Westwick J., Webb H. Selective antagonism of prostaglandin (PG) E1, PGD2 and prostacyclin (PGI2) on human and rabbit platelets by di-4-phloretin phosphate (DPP). Thromb Res. 1978 Jun;12(6):973–978. doi: 10.1016/0049-3848(78)90053-1. [DOI] [PubMed] [Google Scholar]

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