The Effect of Oral Contraceptives on Platelet Noradrenaline and 5-Hydroxytryptamine Receptors and Aggregation

  • J. R. Peters
  • J. M. Elliott
  • D. G. Grahame-Smith

Abstract

Noradrenaline (NA) and 5-hydroxytryptamine (5HT) cause platelet aggregation in vitro, and they enhance aggregation produced by ADP (Mills & Roberts, 1967), collagen and thrombin (Yu & Latour, 1977). There is evidence that platelet membranes possess receptor sites for NA and 5HT. This evidence comes both from functional studies on platelet aggregation and uptake, and from results of radioligand binding techniques which are being used increasingly to demonstrate receptor sites for hormones, neurotransmitters and drugs in various tissues (Tell, Haour & Saez, 1978). The latter technique may enable characteristics of the molecular site of action of a hormone or drug to be examined in some detail and provides a new method for studying aspects of hormone and drug action clinically. Alterations in receptor characteristics have been noted in a number of human disorders (Bar & Roth, 1977; Kaywin, McDonough, Insel & Shattil, 1978).

Keywords

Noradrenaline Progesterone Oestradiol Adrena Line Thrombin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alexander, R. W., Cooper, B. & Handin, R. I. (1978). Characterisation of the human platelet alpha-adrenergic receptor. Correlation of [3H]-dihydroergocryptine binding with aggregation and adenylate cyclase inhibition. J. clin. Invest., 61, 1136–1144.PubMedCentralCrossRefPubMedGoogle Scholar
  2. Bar, R. S. & Roth, J. (1977). Insulin receptor status in disease states of man. Arch. Int. Med., 137, 474–481.CrossRefGoogle Scholar
  3. Biegon, A., Bercovitz, H. & Samuel, H. (1980). Serotonin receptor concentration during the estrous cycle of the rat. Brain Res., 187, 221–225.CrossRefPubMedGoogle Scholar
  4. Boullin, D. J. & Elliott, J. M. (1979). Binding of [3H]-dihydroergocryptine to α-adrenoceptors on intact human platelets. Brit. J. Pharmac., 66, 89p.Google Scholar
  5. Boullin, D. J., Glenton, P. A. M., Molyneux, D., Peters, J. R. & Roach, B. (1977). Binding of 5-hydroxytryptamine in human blood platelets. Brit. J. Pharmac., 61, 453p.Google Scholar
  6. Boullin, D. J., Green, R. A. & Price, K. S. (1972). The mechanism of adenosine diphosphate induced platelet aggregation: binding to platelet receptors and inhibition of binding and aggregation by prostaglandin EI. J. Physiol., 221, 415–426.PubMedCentralCrossRefPubMedGoogle Scholar
  7. Buller, R. E. & O’Malley, B. W. (1976). The biology and mechanism of steroid hormone receptor interaction with the eukaryocytic nucleus. Biochem. Pharmac., 25, 1–12.CrossRefGoogle Scholar
  8. Ciaraldi, T. P. & Marinetti, G. V. (1978). Hormone action at the membrane level; VIII: Adrenergic receptors in the rat heart and adipocytes and their modulation by thyroxine. Biochim. Biophys. Acta, 541, 334–346.CrossRefPubMedGoogle Scholar
  9. Cooper, B., Handin, R. I., Young, L. H. & Alexander, R. W. (1978). Agonist regulation of the human platelet alpha-adrenergic receptor. Nature, 274, 703–706.CrossRefPubMedGoogle Scholar
  10. Drummond, A. H. & Gordon, J. L. (1975a). Inhibition of 5-hydroxy-[3H]-tryptamine binding to rat blood platelets by 5HT antagonists and uptake inhibitors. Brit. J. Pharmac., 55, 275p.Google Scholar
  11. Drummond, A. H. & Gordon, J. L. (1975b). Specific binding sites for 5-hydroxytryptamine on rat blood platelets. Biochem. J., 150, 129–132.PubMedCentralCrossRefPubMedGoogle Scholar
  12. Elliott, J. M., Peters, J. R. & Grahame-Smith, D. G. (1980). The effect of oestrogens and progesterone on α-adrenergic and serotin receptors in rabbit platelets. Eur. J. Pharmac., in press.Google Scholar
  13. Greenberg, D. A. & Snyder, S. H. (1977). Selective labelling of α-adrenergic receptors in rat brain with [3H]-dihydroergocryptine. Life Sci., 20, 927–932.CrossRefPubMedGoogle Scholar
  14. Kaywin, P., McDonough, M., Insel, P. A. & Shattil, S. J. (1978). Platelet function in essential thrombocythemia: decreased epinephrine responsiveness associated with a deficiency of platelet α-adrenergic receptors. New Eng. J. Med., 299, 505–509.CrossRefPubMedGoogle Scholar
  15. Lee, C. Y. & Ryan, R. J. (1974). Estrogen stimulation of human chorionic gonadotrophin binding by luteinised rat ovarian slices. Endocrinology, 95, 1691–1693.CrossRefPubMedGoogle Scholar
  16. Mills, D. C. B. & Roberts, G. C. (1967). Effects of adrenaline on human blood platelets. J. Physiol., 193, 443–453.PubMedCentralCrossRefPubMedGoogle Scholar
  17. Peters, J. R. & Grahame-Smith, D. G. (1980). Receptors on human platelets: characterisation and functional associations. Eur. J. Pharmac., in press.Google Scholar
  18. Roberts, J. M, Insel, P. A., Goldfien, R. D. & Goldfien, A. (1977). α-adrenoceptors but not β-adrenoceptors increase in rabbit uterus with oestrogen. Nature, 270, 624–625.CrossRefPubMedGoogle Scholar
  19. College of General Practitioners (1977). Mortality among oral contraceptive users. Lancet, 2, 727.Google Scholar
  20. Shih, J. C. & Young, H. (1978). The alteration of serotonin binding sites in aged human brain. Life Sci., 23, 1441–1448.CrossRefPubMedGoogle Scholar
  21. Sneddon, J. M. (1969). Sodium-dependent accumulation of 5-hydroxytryptamine by rat blood platelets. Brit. J. Pharmac., 37, 680–688.CrossRefGoogle Scholar
  22. Snedecor, G. W. & Cochran, W. G. (1967). Statistical Methods. Iowa: State University Press.Google Scholar
  23. Stahl, S. & Meltzer, H. Y. (1978). A kinetic and pharmacological analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: comparison with central serotonergic neurons. J. Pharmac. exp. Ther., 205, 118–132.Google Scholar
  24. Tell, G. P., Haour, F. & Saez, J. M. (1978). Hormonal regulation of membrane receptors and cell responsiveness: a review. Metabolism, 27, 1567–1592.CrossRefGoogle Scholar
  25. Tsai, B. S. & Lefkowitz, R. J. (1978). Agonist-specific effects of monovalent and divalent cations on adenylate cyclase-coupled α-adrenergic receptors in rabbit platelets. Mol. Pharmac., 14, 540–548.Google Scholar
  26. Vessey, M. P., McPherson, K. & Johnson, B. (1977). Mortality among women participating in the Oxford/Family Planning Association Contraceptive Study. Lancet, 2, 731–733.CrossRefPubMedGoogle Scholar
  27. Williams, L. T., Lefkowitz, R. J., Watanabe, A. M, Hathaway, D. R. & Besch, H. R. (1977). Thyroid hormone regulation of β-adrenergic receptor number. J. biol. Chem., 252, 2787–2789.PubMedGoogle Scholar
  28. Yu, S. K. & Latour, J. G. (1977). Potentiation by a and inhibition by β-adrenergic stimulations of rat platelet aggregation: a comparative study with human and rabbit platelets. Thromb. Haemost, 37, 413–429.PubMedGoogle Scholar

Copyright information

© The contributors 1980

Authors and Affiliations

  • J. R. Peters
    • 1
  • J. M. Elliott
    • 1
  • D. G. Grahame-Smith
    • 1
  1. 1.MRC Unit and University Department of Clinical PharmacologyRadcliffe InfirmaryOxfordUK

Personalised recommendations