Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 May;91(1):223–227. doi: 10.1111/j.1476-5381.1987.tb09002.x

Binding of thromboxane A2/prostaglandin H2 agonists to human platelets.

P V Halushka, P J Kochel, D E Mais
PMCID: PMC1853501  PMID: 3594077

Abstract

The competition of [125I]-9, 11 dimethylmethano-11, 12 methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza 15 alpha beta-omega-tetranor-thromboxane A2 ([125I]-PTA-OH), a thromboxane A2/prostaglandin H2 receptor antagonist, with a series of thromboxane A2/prostaglandin H2 (TXA2/PGH2) mimetics for binding to the putative TXA2/PGH2 receptor in washed human platelets was studied. The rank order potency for the series of mimetics to compete with [125I]-PTA-OH for binding was compared with their rank order potency for induction of platelet aggregation. The rank order potency for the mimetics to compete with [125I]-PTA-OH for binding was ONO-11113 greater than SQ-26655 greater than U44069 greater than U46619 = 9, 11-azo PGH2 greater than MB28767. This rank order potency was highly correlated with their rank order potency for inducing platelet aggregation (r = 0.992). Changes in the intra or extracellular concentrations of Na+ did not have a significant effect on the competition between U46619 and [125I]-PTA-OH for binding to the putative receptor. In summary, it appears that these TXA2/PGH2 mimetics activate human platelets through the putative TXA2/PGH2 receptor.

Full text

PDF
223

Selected References

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

  1. Armstrong R. A., Jones R. L., Wilson N. H. Ligand binding to thromboxane receptors on human platelets: correlation with biological activity. Br J Pharmacol. 1983 Aug;79(4):953–964. doi: 10.1111/j.1476-5381.1983.tb10541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  4. Claesson H. E., Malmsten C. On the interrelationship of prostaglandin endoperoxide G2 and cyclic nucleotides in platelet function. Eur J Biochem. 1977 Jun 1;76(1):277–284. doi: 10.1111/j.1432-1033.1977.tb11593.x. [DOI] [PubMed] [Google Scholar]
  5. Coleman R. A., Humphrey P. P., Kennedy I., Levy G. P., Lumley P. Comparison of the actions of U-46619, a prostaglandin H2-analogue, with those of prostaglandin H2 and thromboxane A2 on some isolated smooth muscle preparations. Br J Pharmacol. 1981 Jul;73(3):773–778. doi: 10.1111/j.1476-5381.1981.tb16814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Connolly T. M., Limbird L. E. Removal of extraplatelet Na+ eliminates indomethacin-sensitive secretion from human platelets stimulated by epinephrine, ADP, and thrombin. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5320–5324. doi: 10.1073/pnas.80.17.5320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connolly T. M., Limbird L. E. The influence of Na+ on the alpha 2-adrenergic receptor system of human platelets. A method for removal of extraplatelet Na+. Effect of Na+ removal on aggregation, secretion, and cAMP accumulation. J Biol Chem. 1983 Mar 25;258(6):3907–3912. [PubMed] [Google Scholar]
  8. Corey E. J., Nicolaou K. C., Machida Y., Malmsten C. L., Samuelsson B. Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3355–3358. doi: 10.1073/pnas.72.9.3355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feinstein M. B., Henderson E. G., Sha'afi R. I. The effects of alterations of transmembrane Na+ and K+ gradients by ionophores (nigericin, monensin) on serotonin transport in human blood platelets. Biochim Biophys Acta. 1977 Jul 14;468(2):284–295. doi: 10.1016/0005-2736(77)90121-3. [DOI] [PubMed] [Google Scholar]
  10. Gerrard J. M., Carroll R. C. Stimulation of platelet protein phosphorylation by arachidonic acid and endoperoxide analogs. Prostaglandins. 1981 Jul;22(1):81–94. doi: 10.1016/0090-6980(81)90055-1. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Hung S. C., Ghali N. I., Venton D. L., Le Breton G. C. Specific binding of the thromboxane A2 antagonist 13-azaprostanoic acid to human platelet membranes. Biochim Biophys Acta. 1983 Feb;728(2):171–178. doi: 10.1016/0005-2736(83)90468-6. [DOI] [PubMed] [Google Scholar]
  13. Limbird L. E., Speck J. L., Smith S. K. Sodium ion modulates agonist and antagonist interactions with the human platelet alpha 2-adrenergic receptor in membrane and solubilized preparations. Mol Pharmacol. 1982 May;21(3):609–617. [PubMed] [Google Scholar]
  14. Mais D. E., Burch R. M., Saussy D. L., Jr, Kochel P. J., Halushka P. V. Binding of a thromboxane A2/prostaglandin H2 receptor antagonist to washed human platelets. J Pharmacol Exp Ther. 1985 Dec;235(3):729–734. [PubMed] [Google Scholar]
  15. Mais D. E., Saussy D. L., Jr, Chaikhouni A., Kochel P. J., Knapp D. R., Hamanaka N., Halushka P. V. Pharmacologic characterization of human and canine thromboxane A2/prostaglandin H2 receptors in platelets and blood vessels: evidence for different receptors. J Pharmacol Exp Ther. 1985 May;233(2):418–424. [PubMed] [Google Scholar]
  16. Morinelli T. A., Niewiarowski S., Kornecki E., Figures W. R., Wachtfogel Y., Colman R. W. Platelet aggregation and exposure of fibrinogen receptors by prostaglandin endoperoxide analogues. Blood. 1983 Jan;61(1):41–49. [PubMed] [Google Scholar]
  17. Motulsky H. J., Insel P. A. Influence of sodium on the alpha 2-adrenergic receptor system of human platelets. Role for intraplatelet sodium in receptor binding. J Biol Chem. 1983 Mar 25;258(6):3913–3919. [PubMed] [Google Scholar]
  18. Narumiya S., Okuma M., Ushikubi F. Binding of a radioiodinated 13-azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species. Br J Pharmacol. 1986 Jun;88(2):323–331. doi: 10.1111/j.1476-5381.1986.tb10208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saussy D. L., Jr, Mais D. E., Burch R. M., Halushka P. V. Identification of a putative thromboxane A2/prostaglandin H2 receptor in human platelet membranes. J Biol Chem. 1986 Mar 5;261(7):3025–3029. [PubMed] [Google Scholar]
  20. Siess W., Boehlig B., Weber P. C., Lapetina E. G. Prostaglandin endoperoxide analogues stimulate phospholipase C and protein phosphorylation during platelet shape change. Blood. 1985 May;65(5):1141–1148. [PubMed] [Google Scholar]
  21. Siess W., Siegel F. L., Lapetina E. G. Arachidonic acid stimulates the formation of 1,2-diacylglycerol and phosphatidic acid in human platelets. Degree of phospholipase C activation correlates with protein phosphorylation, platelet shape change, serotonin release, and aggregation. J Biol Chem. 1983 Sep 25;258(18):11236–11242. [PubMed] [Google Scholar]
  22. Tsai B. S., Lefkowitz R. J. Agonist-specific effects of monovalent and divalent cations on adenylate cyclase-coupled alpha adrenergic receptors in rabbit platelets. Mol Pharmacol. 1978 Jul;14(4):540–548. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES