Advertisement

6-Keto-Prostaglandin E1: Biosynthesis and Circulatory Effects

  • Eric G. Spokas
  • John C. Mcgiff
  • Patrick Y.-K. Wong
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 54)

Abstract

The changes in circulatory function induced by 6-keto-prostaglandin E1 (6-keto-PGE1) bear a close resemblance to the changes caused by prostacyclin (PGI2). Like PGI2, 6-keto-PGE1 is potent in stimulating renin secretion [l–3], inhibiting platelet aggregation [4], and reducing blood pressure and vascular resistance in diverse regional circulations [5, 6]. In this chaper, we present evidence that 6-keto-PGE1 may arise during the course of metabolic transformation of PGI2 through the activity of 9-hydroxyprostaglandin dehydrogenase (9-OH PGDH) identified in various tissues, including liver, blood platelets, and renal cortex. As PGI2 is unstable, having a half-life of approximately 3 min in aqueous solution [7], the identification of an active and stable metabolite of prostacyclin has important implications for understanding the time-dependency of prostacyclin-induced physiologic responses. In contrast to PGI2, when 6-keto-PGE1 is incubated in aqueous solution at pH 7.4, 37°C its platelet antiaggregatory activity remains undiminished for at least 20 min [3].

Keywords

Platelet Aggregation Human Platelet Renal Cortex Inhibit Platelet Aggregation Renin Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    E. G. Spokas, N. R. Ferreri, P. Y-K Wong, and J. C. McGiff, Circulation, 62 (III): 287 (1980).Google Scholar
  2. 2.
    E. K. Jackson, W. A. Herzer, J. B. Zimmerman, R. A. Branch, J. A. Oates, and J. F. Gerkens, J. Pharmacol. Exp. Ther., 216: 24–27 (1981).Google Scholar
  3. 3.
    J. C. McGiff, E. G. Spokas, and P. Y.-K Wong, Br. J. Pharmacol. 75: 137–144 (1982).PubMedGoogle Scholar
  4. 4.
    P. Y-K Wong, J. C. McGiff, F. F. Sun, and W. H. Lee, Eur. J. Pharmacol., 60: 245–248 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    C. P. Quilley, P. Y-K Wong, and J. C. McGiff, Eur. J. Pharmacol., 57: 273–276 (1979).PubMedCrossRefGoogle Scholar
  6. 6.
    L. P. Feigen, B. M. Chapnick, A. L. Hyman, L. Kind, B. Maras-calco, and P. J. Kadowitz, J. Pharmacol. Exp. Ther., 214: 528534 (1980).Google Scholar
  7. 7.
    M. J. Cho and M. A. Allen, Prostaglandins, 15: 943–954 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    P. Y-K Wong, J. C. McGiff, F. F. Sun, and K. U. Malik, Biochem. Biophys. Res. Commun., 83: 731–738 (1978).CrossRefGoogle Scholar
  9. 9.
    J. F. Gerkens, G. C. Friesinger, R. A. Branch, D. G. Shand, and J. G. Gerber, Life Sciences, 22: 1837–1842 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    A. Szczeklick, R. J. Gryglewski, E. Nizankowska, R. Nizankowski, and J. Musial, Prostaglandins, 16: 651–659 (1978).CrossRefGoogle Scholar
  11. 11.
    E. A. Higgs, G. A. Higgs, S. Moncada, and J. R. Vane, Br. J. Pharmacol., 63: 535–539 (1978).PubMedGoogle Scholar
  12. 12.
    A. R. Whorton, K. Misono, J. Hollifield, J. C. Frolich, T. Inagami, and J. A. Oates, Prostaglandins, 14: 1095–1104 (1977).PubMedCrossRefGoogle Scholar
  13. 13.
    P. Y-K Wong, K. U. Malik, D. M. Desiderio, J. C. McGiff, and F. F. Sun, Biochem. Biophys. Res. Commun., 93: 486–494 (1980).CrossRefGoogle Scholar
  14. 14.
    R. J. Shebuski and J. W. Aiken, J. Cardiovasc. Pharmacol., 2: 667–677 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Y-K Wong and J. C. McGiff, Biochim. Biophys. Acta, 500: 436–439 (1977).CrossRefGoogle Scholar
  16. 16.
    E. K. Jackson and R. P. Goodman, N. Eng. J. Med., 305: 287 (1981).Google Scholar
  17. 17.
    J. Webster, C. N. Hensby, K. Crowley, and C. T. Dollery, 7th Sci. Meet. Int. Soc. Hypertension, New Orleans, p. 142 (1980).Google Scholar
  18. 18.
    G. Masotti, L. Poggesi, G. Galanti, R. Abbate, and G. G. Neri Serneri, Lancet, 2: 1213–1216 (1979).PubMedCrossRefGoogle Scholar
  19. 19.
    A. I. Schafer, B. Cooper, D. O’Hara, R. I. Handin, J. Biol. Chem., 254: 2914–2917 (1979).PubMedGoogle Scholar
  20. 20.
    P. Y-K Wong, W. H. Lee, P. H-W Chao, R. F. Reiss, and J. C. McGiff, J. Biol. Chem., 255: 9021–9024 (1980).PubMedGoogle Scholar
  21. 21.
    C. Pace-Asciak, J. Biol. Chem., 250: 2789–2794 (1975).PubMedGoogle Scholar
  22. 22.
    P. K. Moore and J. R. S. Hoult, Biochim. Biophys. Acta, 528: 276–287 (1978).CrossRefGoogle Scholar
  23. 23.
    H. H. Tai and B. Yuan, Anal. Biochem., 78: 410–422 (1977).PubMedCrossRefGoogle Scholar
  24. 24.
    J. M. Armstrong, N. Lattimer, S. Moncada, and J. R. Vane, Br. J. Pharmacol., 72: 125–130 (1978).Google Scholar
  25. 25.
    R. Flower, in: “Prostacyclin” (J. R. Vane and S. Bergstrom, eds.), Raven Press, New York, p. 130 ( Discussion ) (1979).Google Scholar
  26. 26.
    M. F. Gimeno, L. Sterin-Borda, E. S. Borda, M. A. Lazzari, and A. L. ‘Gimeno, Prostaglandins, 19: 907–916 (1980).PubMedCrossRefGoogle Scholar
  27. 27.
    J. R. S. Hoult, F. J. Lofts, and P. K. Moore, Proc. Br. J. Pharmacol. Soc., 73: 218P (1981).Google Scholar
  28. 28.
    A. L. Hyman and P. J. Kadowitz, J. Pharmacol. Exp. Ther., 213: 468–474 (1980).Google Scholar
  29. 29.
    E. W. Spannhake, J. L. Levin, A. L. Hyman, and P. J. Kadowitz, Prostaglandins, 21: 267–275 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    H. L. Lippton, B. M. Chapnick, A. L. Hyman, and P. J. Kadowitz, Prostaglandins, 19: 299–310 (1980).PubMedCrossRefGoogle Scholar
  31. 31.
    N. S. Rapp, T. V. Zenser, and B. B. Davis, Biochim. Biophys. Acta, 673: 163–169 (1981).CrossRefGoogle Scholar
  32. 32.
    R. Mastacchi, S. Fadda, V. Tomasi, and O. Barnabei, Prostaglandins and Medicine, 5: 487–494 (1980).PubMedCrossRefGoogle Scholar
  33. 33.
    V. Miller, J. W. Aiken, R. J. Shebuski, and R. R. Gorman, Prostaglandins, 20: 391–400 (1980).CrossRefGoogle Scholar
  34. 34.
    J. B. Smith, M. L. Ogletree, A. M. Lefer, and K. C. Nicolaou, Nature, 274: 64–65 (1978).PubMedCrossRefGoogle Scholar
  35. 35.
    D. Maclntyre, M. Steer, B. Galgoci, J. Khorana, L. Levine, and E. Salzman, 4th International Prostaglandin Conference, Washington, D.C., p. 73 (1979).Google Scholar
  36. 36.
    M. H. Weinberger, W. Aoi, and D. P. Henry, Circ. Res., 37: 318324 (1975).Google Scholar
  37. 37.
    U. Schwertschlag and E. Hackenthal, International Symposium on Arachidonic Acid Metabolites and the Kidney, Rome, p. 23 (1981) (Abstract).Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Eric G. Spokas
    • 1
  • John C. Mcgiff
    • 1
  • Patrick Y.-K. Wong
    • 1
  1. 1.Department of PharmacologyNew York Medical CollegeValhallaUSA

Personalised recommendations