Skip to main content

Metabolism of Prostaglandins and Thromboxanes

  • Chapter
The Prostaglandin System

Part of the book series: NATO Advanced Study Institutes Series ((ASIAS))

Abstract

Around 15 years ago the first metabolic steps in the inactivation of prostaglandins were elucidated. It was demonstrated that PGs of the E and F type were extensively taken up by many organs and tissues in the body (see (1) and references therein), mainly by the liver, kidney and lungs, and were inactivated by a few metabolic steps.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. B. Samuelsson, E. Granström, K. Green, M. Hamberg and S. Hammarström, Prostaglandins. Ann. Rev. Biochem. 44:669 (1975).

    Google Scholar 

  2. M. Hamberg and B. Samuelsson, On the metabolism of prostaglandins El and E2 in man. J. Biol. Chem. 246:6713 (1971).

    Google Scholar 

  3. E. Granström and B. Samuelsson, On the metabolism of prostaglandin F2a in female subjects: structures of two metabolites in blood. Eur. J. Biochem. 27:462 (1972).

    Google Scholar 

  4. E. Granström and H. Kindahl, Radioimmunologic determination of 15-keto-13,14-dihydro-PGE2: a method for its stable degradation product, 11-deoxy-13,14-dihydro-15-keto-11ß,16cyclo-prostaglandin E2. In: “Advances in Prostaglandin and Thromboxane Research”, Vo1. 6, Eds. B. Samuelsson, P. Ramwell, R. Pooletti,Raven Press, New York (1980) p. 181.

    Google Scholar 

  5. E. Daniels, W. Krueger, F. Kupiecki, J. Pike and W. Schneider, Isolation and characterization of a new prostaglandin isomer. J. Amer. Chem. Soc. 90:5849 (1968).

    Google Scholar 

  6. M. Hamberg and U. Israelsson, Metabolism of prostaglandin E2 in guinea pig liver. Identification of seven metabolites. J. Biol. Chem. 245:5107 (1970).

    Google Scholar 

  7. L. Cagen, J. Pisano, J. Ketley, W. Habig and W. Jakoby, The conjugation of prostaglandin Al and glutathione catalyzed by homogenous glutathione S-transferases from human and rat liver. Biochim. Biophys. Acta 398:205 (1975).

    Google Scholar 

  8. A. Chaudhari, M. Anderson and T. Eling, Conjugation of 15-keto prostaglandins by glutathione S-transferases. Biochim. Biophys. Acta 531:56 (1978).

    Google Scholar 

  9. M. Hamberg and B. Samuelsson, Metabolism of prostaglandin E2 in guinea pig liver. Pathways in the formation of the major metabolites. J. Biol. Chem. 246:1073 (1971).

    Google Scholar 

  10. E. Granström, Structures of C14 metabolites of prostaglandin F2a. Adv. Biosci. 9:7 (1973).

    Google Scholar 

  11. M. Hamberg and M. Wilson, Structures of new metabolites of Prostaglandin E2 in man. Ibid, p. 39 (1973).

    Google Scholar 

  12. F. Sun and J. Stafford, Metabolism of prostaglandin F2a in Rhesus monkeys. Biochim. Biophys.Acta 369:95 (1974).

    Google Scholar 

  13. C. Ellis, M. Smigel, J. Oates, 0. Oelz and S. Sweetman, Metabolism of prostaglandin D2 in the monkey. J. Biol. Chem. 254:4152 (1979).

    Google Scholar 

  14. E. Granström and B. Samuelsson, Quantitative measurement of prostaglandins and thromboxanes: General considerations. In: “Advances in Prostaglandin and Thromboxane Research”. Vol. 5, Ed. J. Frölich, Raven Press, New York, (1978), pp. 1–13.

    Google Scholar 

  15. C. Leslie and L. Levine, Evidence for the presence of a prostaglandin E2 9-ketoreductase in rat organs. Biochem. Biophys. Res. Commun. 52:717 (1973).

    Google Scholar 

  16. K. Stone and M. Hart, Prostaglandin E2–9-ketoreductase in rabbit kidney. Prostaglandins 10: 273 (1975).

    CAS  Google Scholar 

  17. C. Pace-Asciak and D. Miller, Prostaglandins during development. II. Identification of prostaglandin 9-hydroxydehydrogenase activity in adult rat kidney. Experientia 30: 590 (1974).

    Article  PubMed  CAS  Google Scholar 

  18. C. Pace-Asciak, Prostaglandins during development. III. Prostaglandin 9-hydroxydehydrogenase activity in the adult rat kidney. Identification, assay, pathway and some properties. J. Biol. Chem. 250:2789 (1975).

    Google Scholar 

  19. P. Moore and J. Moult, Distribution of four prostaglandin-metabolising enzymes in organs of the rabbit. Biochem. Pharmacol. 27:1839 (1978).

    Google Scholar 

  20. P. Wong, K. Malik, F. Sun, W. Lee and J. McGiff, Hepatic metabolism of PGI2 in the rabbit: Formation of a potent inhibitor of platelet aggregation. Abstr. IV International Prostaglandin Conference, Washington D.C., May 1979.

    Google Scholar 

  21. J. Weeks, D. Ducharme, W. Magee, W. Miller, The biological activity of the (15s)-15-methyl analogs of prostaglandins E2 and Fla J. Pharmacol. Exp. Ther. 186:67 (1973).

    Google Scholar 

  22. B. Magerlein, D. Ducharme, W. Magee, W. Miller, A. Robert and J. Weeks, Synthesis and biological properties of 16alkyl-prostaglandins. Prostaglandins 4: 143 (1973).

    CAS  Google Scholar 

  23. B. Magerlein and W. Miller, 16-Fluoroprostaglandins. Prostaglandins 9: 527 (1975).

    Google Scholar 

  24. H. Ohno, Y. Morikawa and F. Hirata, Studies on 15-hydroxyprostaglandin dehydrogenase with various prostaglandin analogues. J. Biochem. 84:1485 (1978).

    Google Scholar 

  25. M. 0. Pulkkinen, Pregnancy termination with the PGE2 analogue SHB 286 Prostaglandins 15: 161 (1978).

    Google Scholar 

  26. D. Binder, J. Bowler, E. Brown, N. Crossley. J. Hutton, M. Senior, L. Slater, P. Wilkinson and N. Wright, 16Aryloxy-prostaglandins: a new class of potent luteolytic agents. Prostaglandins 6: 87 (1974).

    CAS  Google Scholar 

  27. K. Green, B. Samuelsson and J. Magerlein, Decreased rate of metabolism induced by a shift of the double bond in prostaglandin Fla from the A5 to the A4 position. Eur. J. Biochem. 62:527 (1976).

    Google Scholar 

  28. G. Tarpley and F. Sun, Metabolism of cis-A4-15(S)-15-methylprostaglandin Flu methyl ester in the rat. J. Med. Chem. 21:288 (1978).

    Google Scholar 

  29. M. Hamberg, J. Svensson and B. Samuelsson, Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. USA 72:2994 (1975).

    Google Scholar 

  30. H. Kindahl, Metabolism of thromboxane B2 in the cynomolgus monkey. Prostaglandins 13: 619 (1977).

    CAS  Google Scholar 

  31. J. Roberts II, B. Sweetman, J. Morgan, N. Payne and J. Oates, Identification of the major urinary metabolite of thromboxane B2 in the monkey. Prostaglandins 13: 631 (1977).

    CAS  Google Scholar 

  32. J. Roberts II, B. Sweetman and J. Oates, Metabolism of thromboxane B2 in the monkey. J. Biol. Chem. 253:5305 (1978).

    Google Scholar 

  33. J. Roberts II, B. Sweetman, N. Payne and J. Oates, Metabolism of thromboxane B2 in man. Identification of the major urinary metabolite. J. Biol. Chem. 252:7415 (1977).

    Google Scholar 

  34. J. Svensson, Structure and quantitative determination of the major urinary metabolite of thromboxane B2 in the guinea pg. Prostaglandins 17: 351 (1979).

    CAS  Google Scholar 

  35. P. Piper and J. Vane, Release of additional factors in anaphylaxis and its antagonism by anti inflammatory drugs, Nature 223: 29 (1969).

    CAS  Google Scholar 

  36. M. Hamberg, J. Svensson, P. Hedqvist, K. Strandberg and B. Samuelsson, Involvement of endoperoxides and thromboxanes in anaphylactic reactions. In: “Advances in Prostaglandin and Thromboxane Research”, B. Samuelsson and R. Paoletti, eds., Raven Press, New York, Vol. 1, pp. 495–501 (1976).

    Google Scholar 

  37. W. Dawson, J. Boot, A. Cockerill, D. Mallen and D. Osborne, Release of novel prostaglandins and thromboxanes after immunological challenge of guinea pig lung. Nature 262: 699 (1976).

    CAS  Google Scholar 

  38. J. Boot, W. Dawson, A. Cockerill, D. Mallen and D. Osborne, The pharmacology of prostaglandin like substances released from guinea pig lungs during anaphylaxis. Prostaglandins 13: 927 (1977).

    CAS  Google Scholar 

  39. J. Boot, A. Cockerill, W. Dawson, D. Mallen and D. Osborne, Modification of prostaglandin and thromboxane release by immunological sensitisation and successive immunological challenges from guinea-pig lung. Int. Arch. Allergy Appl. Immunol. 57:159 (1978).

    Google Scholar 

  40. F. Fitzpatrick and R. Gorman, Platelet rich plasma tranforms exogenous prostaglandin H2 into thromboxane A2. Prostaglandins 14: 881 (1977).

    Google Scholar 

  41. J. Maclouf, H. Kindahl, E. Granström and B. Samuelsson, Thromboxane A2 and prostaglandin endoperoxide H2 form covalently linked derivatives with human serum albumin. In: “Advances in Prostaglandin and Thromboxane Research”, Vol. 6, Eds. B. Samuelssen, P. Ramwell, R. Pooletti, Raven Press, New York (1980) p. 283.

    Google Scholar 

  42. G. Folco, E. Granström and H. Kindahl, Albumin stabilizes thromboxane A2. FEBS Lett 82: 321 (1977).

    Article  CAS  Google Scholar 

  43. J. Smith, C. Ingerman and M. Silver, Persistence of thromboxane A2-like material and platelet release-inducing activity in plasma. J. Clin. Invest. 58:1119 (1976).

    Google Scholar 

  44. C. Pace-Asciak, M. Carrara and Z. Domazet, Identification of the major urinary metabolites of 6-keto-prostaglandin Fia (6K-PGFia) in the rat. Biochem. Biophys. Res. Commun. 78:115 (1977).

    Google Scholar 

  45. C. Pace-Asciak, Z. Domazet and M. Carrara, Catabolism of 6-keto-prostaglandin Fin by the rat kidney cortex. Biochim. Biophys. Acta 487:400 (1977).

    Google Scholar 

  46. J. McGuire and F. Sun, Metabolism of prostacyclin. Oxidation by rhesus monkey lung 15-hydroxyl prostaglandin dehydrogenase. Arch. Biochem. Biophys. 189:92 (1978).

    Google Scholar 

  47. F. Sun and B. Taylor, Metabolism of prostacyclin in rat. Biochemistry 17: 4096 (1978).

    CAS  Google Scholar 

  48. F. Sun, B. Taylor, D. Sutter and J. Weeks, Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGFla in rat. Prostaglandins 17: 753 (1979).

    PubMed  CAS  Google Scholar 

  49. G. Dusting, S. Moncada and J. Vane, Recirculation of prostacyclin (PGI2) in the dog. Br. J. Pharmac. 64:315 (1978).

    Google Scholar 

  50. P. Wong, J. McGiff, F. Sun and K. Malik, Pulmonary metabolism of prostacyclin (PGI2) in the rabbit. Biochem. Biophys. Res. Commun. 83:731 (1978).

    Google Scholar 

  51. H. Hawkins, J. Smith, K. Nicolaou and T. Eling, Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 6-keto-PGFla in the pulmonary circulation. Prostaglandins 16: 871 (1978).

    CAS  Google Scholar 

  52. P. Wong, F. Sun and J. McGiff, Metabolism of prostacyclin in blood vessels. J. Biol. Chem. 253:5555 (1978).

    Google Scholar 

  53. P. Wong, J. McGiff, L. Cagen, K. Malik and F. Sun, Metabolism of prostacyclin in the rabbit kidney. J. Biol. Chem. 254: 12 (1979).

    Google Scholar 

  54. A. Cockerill, D. Mallen, D. Osborne, J. Boot and W. Dawson, The identification of two novel prostaglandins and a thromboxane. Prostaglandins 13: 1033 (1977).

    CAS  Google Scholar 

  55. S. Moncada, R. Korbut, S. Bunting and J. Vane, Prostacyclin is a circulating hormone. Nature 273: 767 (1978).

    CAS  Google Scholar 

  56. H. Waldman, I. Alter, P. Kot, J. Rose and P. Ramwell, Effect of lung transit on systemic depressor responses to arachidonic acid and prostacyclin in dogs. J. Pharmacol. Exp. Ther. 204:289 (1978).

    Google Scholar 

  57. B. Taylor and F. Sun, Hepatic metabolism of prostacyclin in the rat. Abstr. IV. International Prostaglandin Conference, Washington D.C., May 1979.

    Google Scholar 

  58. P. Needleman, S. Bronson, A. Wycke, M. Sivakoff and K. Nicolaou, Cardiac and renal prostaglandin I2. Biosynthesis and biological effects in isolated perfused rabbit tissues. J. Clin. Invest. 61:839 (1978).

    Google Scholar 

  59. C. Pace-Asciak and A. Rosenthal, Comparison between the in vivo rates of matabolism of PGI2 and its blood pressure lowering effect after intravenous administration in the rat. Abstr. IV International Prostaglandin Conference, Washington D.C., May 1979.

    Google Scholar 

  60. R. Gryglewski, R. Korbut, A. Ocetkiewicz and T. Stachwa, In vivo method for quantitation of anti-platelet potency of drugs. Naunyn-Schmiedebergs Archs.Pharmacol 302:25 (1978).

    Google Scholar 

  61. F. Sun, K. Malik, J. McGiff and P. Wong, Evidence for a one carbon degradation pathway in the metabolism of PGI2 by rabbit kidney. Abstr. IV International Prostaglandin Conference, Washington D.C., May 1979.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1981 Plenum Press, New York

About this chapter

Cite this chapter

Granström, E. (1981). Metabolism of Prostaglandins and Thromboxanes. In: Berti, F., Velo, G.P. (eds) The Prostaglandin System. NATO Advanced Study Institutes Series. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-3896-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-3896-3_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-3898-7

  • Online ISBN: 978-1-4684-3896-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics