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Generation of Prostaglandin and Thromboxane-Like Substances by Large Airways and Lung Parenchyma

  • R. J. Gryglewski
  • A. Dembińska-Kieć
  • L. Grodzińska
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 13)

Abstract

Anggard and Samuelsson (1965) were the first researchers to study the biosynthesis of prostaglandins in lungs. They found that the low speed supernatant (900 × g) of a homogenate of guinea pig lungs incubated with arachidonic acid converted 10% of the substrate to more polar products than arachidonic acid. These products were identified as PGF, PGE2 and their metabolites. Guinea pig lung homogenates were used by Vane (1971) in his work that lead to the discovery of the anti-prosta-glandin synthetase activity of aspirin like drugs. In rat lung homogenates dihomo-γ-linolenic acid is mainly converted to PGD1, similarily as prostaglandin endoper-oxides PGH1 and PGH2 are chiefly metabolized to PGD1 and PGD2, respectively (Nugteren and Hazelhof, 1973). Further studies on metabolism of radioactive arachidonic acid by whole homogenates of guinea pig lungs brought to unexpected results (Hamberg and Samuelsson, 1974). The formation of PGF2 and PGE2, both in 2–3% yield was confirmed.

Keywords

Lung Parenchyma Airway Smooth Muscle Rabbit Aorta Prostaglandin Endoperoxide Aortic Strip 
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.

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References

  1. Anggard, E., and Samuelsson B., 1965. Biosynthesis of prostaglandins from arachidonic acid in guinea pig lung. J. Biol. Chem. 240: 3518–3521.PubMedGoogle Scholar
  2. Bakhle, Y.S., and Smith, T.W., 1972. Release of spasmogenic substances induced by vasoactive amines from isolated lungs. Br. J. Pharmac. 46: 543–544.Google Scholar
  3. Bouhuys, A., 1975. Prostaglandins ancPasthma. Lancet 1: 399.PubMedCrossRefGoogle Scholar
  4. Bouhuys, A., Douglas, J.S., and Brink, C., 1976. Actions of chemical mediators and drugs on effector cells. Pneurnonologie 153: 148–149.Google Scholar
  5. Bunting, S., Moncada, S., and Vane, J.R., 1976. The effects of prostaglandin endoperoxides and thromboxane A2 on strips of rabbit coeliac artery and certain other smooth muscle preparations, Proc. Br. Pharmacol. Soc. 1–2 April, p. 48.Google Scholar
  6. Coburn, R.F., Hizig, B., and Yamaguchi, T., 1974. Prosta qlandin (PG) synthesis in canine trachealis muscle (CTM) and guinea pig taenia coli (TC). Fed. Proc. 33: 451.Google Scholar
  7. Dunlop, L.S., and Smith, A.P., 1975. Reduction of antigen-induced contractions of sensitized human bronchus in vitro by indomethacin. Br. J. Pharmac. 54: 495–497.Google Scholar
  8. Fjalland, B., 1974, Inhibition by non-steroidal antiinflammatory agents of the release of rabbit aorta contracting substance and prostaglandins from chopped guinea pig lungs. 3. Pharm. Pharmacol. 26: 448–451.Google Scholar
  9. Gilmore, N., Vane, J.R., and Wyllie, J.H., 1968, Prostaglandins released by the spleen. Nature 218: 1135–1140.PubMedCrossRefGoogle Scholar
  10. Grodzińska, L., Panczenko, B., and Gryglewski, R.I., 1975, Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine. 3. Pharm. Pharmac. 27: 88–91.CrossRefGoogle Scholar
  11. Gryglewski, R.J., Dembińska-kieć, A., Grodzińska, L., and Panczenko, B., 1976, Differential generation of substances with prostaglandin-like and thromboxane-like activities by guinea pig trachea and by lung strips, in:Lung cells in disease (A. Bouhuys, ed.), in press. Elsevier Pub. Amsterdam.Google Scholar
  12. Gryglewski, R.J., Panczenko, B., Korbut, R., Grodzinska, L., and Ocetkiewicz, A., 1975, Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins 10: 343–355.PubMedGoogle Scholar
  13. Gryglewski, R., and Vane, J.R., 1972a, The release of prostaglandins and rabbit aorta contracting substance (RCS) from rabbit spleen and its antagonism by anti-inflammatory drugs. Br. 3. Pharmac. 45: 37–47.Google Scholar
  14. Gryglewski, R., and Vane, J.R., 1972b, The generation from arachidonic acid of rabbit aorta contracting substance (RCS) by microsomal enzyme preparation which also generates prostaglandins. Br. 3. Pharmac. 46: 449–457.Google Scholar
  15. Hamberg, M., and Samuelsson, B., 1973, Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc. Nat. Acad. Sci. USA 70: 899–903.PubMedCrossRefGoogle Scholar
  16. Hamberg, M., and Samuelsson, B., 1974, Prostaglandin endoperoxides VII. Novel transformations of arachidonic acid in guinea pig ludg. Biochem. Biophys. Res. Commun. 61; 942–949.PubMedCrossRefGoogle Scholar
  17. Hamberg, M., Svensson, J., and Samuelsson, B., 1975, Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides, Proc. Nat. Acad. Sci. USA, 72: 2994–2998.PubMedCrossRefGoogle Scholar
  18. Kaliner, M., and Austen, K.F., 1975, Immunologic release of chemical mediators from human tissues in: Annual Review of Pharmacology (H.W. Elliot, R. George and R. Okum, eds.), pp. 177–189. Annual Review Inc. California.Google Scholar
  19. Kapanci, Y., and Gabbiani, G., 1976, Location and function of contractile interstitial cells of the lung. Pneumonologie 153: 141.Google Scholar
  20. Malmsten, C., 1976, Some biological effects of prostaglandin endoperoxide analogs. Life Sci. 18: 169–176.PubMedCrossRefGoogle Scholar
  21. Mathe’, A.A., and Levine, L., 1973, Release of prostaglandins and metabolites from guinea pig lungs: inhibition by catecholamines. Prostaglandins 4: 877–890.CrossRefGoogle Scholar
  22. Needleman, P., Moncada, S., Bunting, S., Vane, J.R., Hamberg, M., and Samuelsson, B., 1976, Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature 261: 558–560.PubMedCrossRefGoogle Scholar
  23. Nugteren, D.H., Hazelhop, E., 1973, Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim. Biophys. Acta 326: 448–461.PubMedGoogle Scholar
  24. Orehek, J., Douglas, J.S., and Bouhuys, A., 1975, Contractile responses of the guinea-pig trachea in vitro: modification by prostaglandin synthesis-inhibiting drugs, J. Pharmacol. 194: 554–564.Google Scholar
  25. Orehek, J., Douglas, J.S., Lewis, A.J., and Bouhuys, A., 1973, Prostaglandin regulation of airway smooth muscle tone. Nature New Biology 245: 84–85.PubMedGoogle Scholar
  26. Palmer, M.A., Piper, P.J., and Vane, J.R., 1970, The release of rabbit aorta contracting substance from chopped lungs and it antagonism by anti-inflammatory drugs. Br. J. Pharmac. 40: 581P–582P.Google Scholar
  27. Palmer, M.A., Piper, P.J., and Vane J.R., 1973, Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea pig lungs. Br.3.Pharmac. 49: 226–242.Google Scholar
  28. Panczenko, B., Grodzińska, L., and Gryglewski, R.J., 1975, The dual action of meclofenamate on the contractile response to PGF2 in the guinea pig trachea. Pol. J. Pharmacol. 27: 273–276.Google Scholar
  29. Piper, P.J., and Vane, J.R., 1969, Release of additional factors in anaphylaxis and its antagonism by antiinflammatory drugs. Nature 233: 29–35.CrossRefGoogle Scholar
  30. Piper, P.J., and Vane, J.R., 1971, The release of prostaglandins from lung and other tissues. N.Y. Acad. Sci. 180: 363–385.CrossRefGoogle Scholar
  31. Sorrentino, L., Capasso, F., Di Rosa, M., 1972, Indometacin and prostaglandins. Europ. J. Pharmac. 17: 306–308.CrossRefGoogle Scholar
  32. Svensson, J., Hamberg, M., Samuelsson, B., 1975, Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets. Acta Physiol. Scand. 94: 222–228.PubMedCrossRefGoogle Scholar
  33. Szczeklik, A., Gryglewski, R.J., and Mysik-Czerniawska, G., 1975, Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. Br. Med. J. 1:67–69.PubMedCrossRefGoogle Scholar
  34. Vane, J.R., 1971, Inhibition of prostaglandin synthesis as a mechanism uf action for aspirin-like drugs. Nature New Biol. 231: 232–235.PubMedGoogle Scholar
  35. Vargaftig, B.B., and Dao Hai, N., 1971, Release of vasoactive substances from guinea-pig lungs by slow reacting substance C and arachidonic acid. Pharmacology 6: 99–108.PubMedCrossRefGoogle Scholar
  36. Vargaftig, B.B., and Zirinis, P., 1973, Arachidonic acid induced platelet aggregation is accompanied by release of potential inflammatory mediators distinct from PGE3 and PGF2 Nature New Biol. 244: 114–116.PubMedGoogle Scholar
  37. Yen, S.S., Mathe’, A.A., and Dugan, J.J., 1976, Release of prostaglandins from healthy and sensitized guinea-pig lung and trachea by histamine. Prostaglandins 11: 227–239.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • R. J. Gryglewski
    • 1
  • A. Dembińska-Kieć
    • 1
  • L. Grodzińska
    • 1
  1. 1.Department of PharmacologyCopernicus Academy of Medicine in CracowCracowPoland

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