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9α,11β-Prostaglandin F2: A New Prostanoid, That Inhibits Platelet Aggregation and Constricts Blood Vessels

  • Xiao Rong He
  • Charles Polsen
  • Patrick Y.-K. Wong
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 177)

Abstract

Nugteren and Hazelhof (1)were the first to report the formation of PGD2 from endoperoxides (PGG2 and PGH2). Subsequently, PGD2 was found to be one of the major products of arachidonic acid cascade in many tissue and cell types (2). Since then the transformation of PGH2 to PGD2 has been demonstrated in brain homogenates (3,4) and neuroblastoma cells (5). The enzyme PGD2 synthetase, which catalyzed the conversion of PGH2 to PGD2, has been purified to homogeneity and clearly distinguished from that of glutathione-S-transferase(6). It has been reported that PGD2 is released by platelets during aggregation (7) and was found to be a potent inhibitor of platelet aggregation, with a potency only less than that of prostacyclin (PGI2) and its stable biologically active metabolite, 6-keto-PGE1 (8,9). The metabolism of prostaglandin D2 in the monkey has been reported by Ellis et al. (10), who found that more than two-thirds of the PGD2 metabolites have the cyclopentane 1,3-diol ring structure (PGF). These workers postulated the existence of an enzyme 11-ketoreductase which may have converted the infused PGD2 to PGF before it was further degraded by 15-hydroxyprostaglandin dehydrogenase and β-oxidation.

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References

  1. D.H. Nugteren and E. Hazelhof, Isolation and properties of intermediates in prostaglandin biosynthesis, Biochim. Biophys. Acta 326:448–461 (1973).CrossRefGoogle Scholar
  2. 2.
    B. Samuelsson, M. Goldyne, E. Granstome, M. Hamberg, S. Hammarstrom and C. Malmsten, Prostaglandins and thromboxanes, Ann. Rev. Biochem. 47:997–1029 (1978).CrossRefGoogle Scholar
  3. 3.
    M. Abdel-Halim, M. Hamberg, B. Sjoquist and E. Anggard, Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain, Prostaglandins 14: 633–643 (1977).PubMedGoogle Scholar
  4. 4.
    F.F. Sun, J.P. Chapman and J.C. McGuire, Metabolism of prostaglandin endoperoxide in animal tissues, Prostaglandins 14: 1055–1074 (1977).PubMedGoogle Scholar
  5. T. Shimizu, N. Mizuro, T.Amano and 0. Hayaishi, Prostaglandin D2, a neuromodulator, Proc. Natl. Acad. Sci. U.S.A. 76:6231–6234 (1979).CrossRefGoogle Scholar
  6. 6.
    E. Christ-Hazelhof and D.H. Nugteren, Purification and characterization of prostaglandin endoperoxide D-isomerase, a cytoplasmic, glutathione-requiring enzyme, Biochim. Biophys. Acta 572:43–51 (1979).CrossRefGoogle Scholar
  7. 7.
    O.Oelz, R. Oelz, H.R. Knapp, B.J. Sweetman and J.A. Oates, Biosynthesis of prostagladnin D2. 1. Formation of prostaglandin D2 by human platelets, Prostaglandins 13: 225–234 (1977).PubMedGoogle Scholar
  8. 8.
    G. DiMinno, M.J. Silver and G. DeGaetano, Prostaglandins as inhibitors of human platelet aggregation, Brit. J. Haemat. 43:637–647 (1979).CrossRefGoogle Scholar
  9. 9.
    P.Y-K Wong, J.C. McGiff, F.F. Sun and W.H. Lee, 6-keto-prostaglandin El inhibits the aggregation of human platelets, Europ. J. Pharmacol. 60:245–248 (1979).CrossRefGoogle Scholar
  10. 10.
    C.K. Ellis, M.D. Smigel, J.A. Oates, 0. Adz and B.J. Sweetman, Metabolism of prostaglandin D2 in the monkey, J Biol. Chem. 254:4152–4163 (1979).PubMedGoogle Scholar
  11. 11.
    P.Y-K Wong, Purification and partial characterization of prostaglandin D2 11-keto-reductase in rabbit liver, Biochim. Biophys. Acta 659:169–178 (1981).CrossRefGoogle Scholar
  12. 12.
    K. Watanabe, T. Shimiza and 0. Hayaishi, Enzymatic conversion of prostaglandin D2 to F2a in the rat lung, Biochem. Int. 2:603–610 (1981).Google Scholar
  13. T.E. Liston and L.J. Roberts II, Transformation of prostagladnin D2 to 9a,11ß-(15S)-trihydroxy-prosta-(5Z,13E)-dien-1-oic acid (9a,11ß-prostaglandin F2): a unique biologically active prostaglandin produced enzymatically in vivo in humans, Proc. Natl. Acad. Sci. U.S.A. 82:6030–6034 (1985).Google Scholar
  14. P.Y-K Wong, K.U. Malik, D.M. Desiderio, J.C. McGiff and F.F. Sun, Hepatic metabolism of prostacyclin (PGI2) in the rabbit: formation of a potent novel inhibitor of platelet aggregation, Biochim. Biophys. Res. Commun. 93:486–494 (1980).CrossRefGoogle Scholar
  15. 15.
    W.L. Powell, Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica, Prostaglandins 20: 947–957 (1980).PubMedGoogle Scholar
  16. C. Pace-Asciak and L.S. Wolfe, N-butylboronate derivatives of the F prostaglandins. Resolution of prostagladnins of the E and F series by gas-liquid chromatography, J. Chromatogr. 56:129–135 (1971).CrossRefGoogle Scholar
  17. 17.
    C.T. Stier, J. Roberts II and P.Y-K Wong, Renal response to 9a,11ß-prostaglandin F2 in the rat, J. Pharmacol. Exp. Therap. 243:487–491 (1987).Google Scholar
  18. 18.
    T.E. Zook and J.W. Strandhoy, Mechanisms of the natriuretic and diuretic effects of prostaglandin Fla, J. Pharmacol. EXP. Ther. 217:674–680 (1981).Google Scholar
  19. 19.
    D.F. Wendelborn, K. Seibert and J. Robert II, Isomeric prostaglandin F2 compounds arising from prostaglandin D2: a family of icosanoids produced in vivo in humans, Proc. Natl. Acad. Sci. U.S.A. 85:304–308 (1988).CrossRefGoogle Scholar
  20. 20.
    A. Nasjletti, A. Erman, L.M. Cagen, D.P. Brooks, J.T. Crofton, L. Share and P.G. Baer, High potassium intake selectively increases urinary PGF2a excretion in the rat, Am. J. Physiol. 248:F382–388 (1985).Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Xiao Rong He
    • 1
  • Charles Polsen
    • 1
  • Patrick Y.-K. Wong
    • 1
  1. 1.Departments of PharmacologyNew York Medical CollegeValhallaUSA

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