Action of Prostaglandins and Other Arachidonic Acid Metabolites on Airway Function

  • M. F. Cuthbert
  • P. J. Gardiner
Part of the NATO Advanced Study Institutes Series book series


The prostaglandins were first isolated from the lungs by Bergstrom and his co-workers in 1962 (1). More recently other metabolites of arachidonic acid have also been isolated from the lungs, namely, thromboxanes (2,3) and prostacyclin (4). It is now established that the prostaglandins, thromboxanes and prostacyclin (prostanoids) have powerful effects on both respiratory and vascular smooth muscle and that the lungs have an important function in their metabolic degradation. The most important enzyme in this respect is 15-prostaglandin dehydrogenase and some 90% of most infused prostaglandins except the PGA’s and PGI2 are removed in a single passage through the pulmonary circulation in both animals and man (5,6). It is understandable that these findings have led to considerable speculation on the possible physiological and pathological role of the prostanoids on respiratory function and has raised the possibility that prostaglandins of the E series or their metabolites, or substances that interfere with the synthesis of action of the prostanoids, might be of therapeutic value in the treatment of certain respiratory disorders, notably in bronchial asthma.


Airway Smooth Muscle Mefenamic Acid Disodium Cromoglycate Prostaglandin Endoperoxide Bronchodilator Activity 


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  1. 1.
    S. Bergstrom, F. Dressler, L. Krabisch, R. Ryhage and J. Sjövall, The isolation and structure of a smooth muscle stimulating factor in normal pig and sheep lungs. Arkiv fur Kemi., 20: 63 (1962).Google Scholar
  2. 2.
    P. J. Piper and J. R. Vane, Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature, 223: 29 (1969).PubMedCrossRefGoogle Scholar
  3. 3.
    M. Ramberg, J. Svensson and B. Samuelsson, Thromboxanes. A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Nat. Acad. Sci. USA., 72: 2994 (1975).CrossRefGoogle Scholar
  4. 4.
    S. Moncada, R. Gryglewski, S. Bunting and J. R. Vane, An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature, 263: 663 (1976).PubMedCrossRefGoogle Scholar
  5. 5.
    P. J. Piper, J. R. Vane and J. H. Wyllie, Inactivation of prostaglandins by the lung. Nature, 225: 600 (1970).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Jose, U. Niederhauser, P. J. Piper, C. Robinson and A. P. Smith, Inactivation of prostaglandin F2a in the human pulmonary circulation. Brit. J. Clin. Pharmacol., 3: 342 (1976).Google Scholar
  7. 7.
    E. Anggard and S. Bergström, Biological effects of an unsaturated tri-hydroxy-acid (PGF2a) from normal swine lung. Acta. Physiol. Scand., 58: 1 (1963).PubMedCrossRefGoogle Scholar
  8. 8.
    I. H. M. Main, The inhibitory actions of prostaglandins on respiratory smooth muscle. Brit. J. Pharmacol., 22: 511 (1964).PubMedGoogle Scholar
  9. 9.
    P. J. Gardiner and H. O. J. Collier, Specific receptors for prostaglandins in the airways. Prostaglandins (in preparation) (1979/80).Google Scholar
  10. 10.
    P. A. Berry and H. O. J. Collier, Bronchoconstrictor action for antagonism of a slow reacting substance from anaphylaxis of guinea-pig isolated lung. Brit. J. Pharmacol., 23: 201 (1964).PubMedGoogle Scholar
  11. 11.
    M. E. Rosenthale, A. Dervinis, A. J. Begany, M. Lapidus and M. I. Gluckman, Bronchodilator activity of prostaglandin E2 when administered by aerosol to three species. Experientia., 26: 1119 (1970).PubMedCrossRefGoogle Scholar
  12. 12.
    M. E. Rosenthale, A. Dervinis and J. Kassarich, Bronchodilator activity of the prostaglandins El & E2. J. Pharmacol. Exp. Ther., 178: 541 (1971).PubMedGoogle Scholar
  13. 13.
    B. J. Large, P. F. Leswell and D. R. Maxwell, Bronchodilator activity of prostaglandin El in experimental animals. Nature, 224: 78 (1969).PubMedCrossRefGoogle Scholar
  14. 14.
    W. J. F. Sweatman and H. O. J. Collier, Effects of prostaglandins on human bronchial muscle. Nature, 217: 69 (1968).PubMedCrossRefGoogle Scholar
  15. 15.
    M. F. Cuthbert, Effect on airways resistance of prostaglandin El given by aerosol to healthy and asthmatic volunteers. Brit. Med. J., 4: 723 (1969).PubMedCrossRefGoogle Scholar
  16. 16.
    A. P. Smith, M. F. Cuthbert and L. S. Dunlop, Effects of inhaled prostaglandins El, E2 and F2a on airways resistance in healthy and asthmatic man. Clinical Science, 48: 421 (1975).Google Scholar
  17. 17.
    P. Hedqvist, A. Holmgren and A. A. Maths, Effect of prostaglandin F2a on airways resistance in man. Acta. Physiol. Scand., 82: 29a (1971).Google Scholar
  18. 18.
    A. P. Smith and M. F. Cuthbert, The antagonistic action of prostaglandins F2a and E2 aerosols on bronchial muscle tone in man. Brit. Med. J., 3: 212 (1972).PubMedCrossRefGoogle Scholar
  19. 19.
    K. R. Patel, Atropine, sodium cromoglycate and thymoxamine in PGF2a induced bronchoconstriction in extrinsic asthma. Brit. Med. J., 2: 360 (1975).PubMedCrossRefGoogle Scholar
  20. 20.
    A. A. Maths, P. Hedqvist, A. Holmgren and N. Svanborg, Bronchial hyperreactivity to prostaglandin F2a and histamine in patients with asthma. Brit. Med. J., 1: 193 (1973).CrossRefGoogle Scholar
  21. 21.
    A. P. Smith, A comparison of the effects of prostaglandin E2 and salbutamol by intravenous infusion on the airways obstruction of patients with asthma. Brit. J. Clin. Pharmacol., 1: 399 (1974).Google Scholar
  22. 22.
    J. Svensson, K. Strandberg, T. Tuvemo and M. Hamberg, Thromboxane A: Effects on airway and vascular smooth muscle. Prostaglandins, 14: 425 (1977).Google Scholar
  23. 23.
    M. A. Wasserman and R. L. Griffin, Thromboxane B2: comparative bronchoactivity in experimental systems. Eur. J. Pharmacol., 46: 303 (1977).PubMedCrossRefGoogle Scholar
  24. 24.
    C. Omini, S. Moncada and J. R. Vane, The effects of prostacyclin (PGI2) on tissues which detect prostaglandins. Prostaglandins, 14: 625 (1977).PubMedGoogle Scholar
  25. 25.
    M. A. Wasserman, D. W. Du Charme, R. L. Griffin, M. G. Wendling and G. L. De Graaf, Bronchial and cardiovascular actions of prostacyclin (PGI2). Pharmacologist, 19: 145 (1977).Google Scholar
  26. 26.
    M. E. Rosenthale, A. Dervinis, J. Kassarich, S. Singer and M. I. Gluckmann, Comparative studies on the bronchodilating properties of prostaglandin F213. Adv. Biosc., 9: 229 (1973).Google Scholar
  27. 27.
    P. Y. Lo, Effects of pulmonary metabolites of prostaglandins E2 and Fla on guinea-pigs respiratory tract. J. Pharm. Pharmacol., 29: 752 (1977).PubMedCrossRefGoogle Scholar
  28. 28.
    W. Dawson, R. L. Lewis, R. E. McMahon and W. J. F. Sweatman, Potent bronchoconstrictor activity of 15-keto-prostaglandin Fla. Nature, 250: 331 (1974).PubMedCrossRefGoogle Scholar
  29. 29.
    D. J. Crutchley and P. J. Piper, Comparative bioassay of prostaglandin E2 and its three pulmonary metabolites. Brit. J. Pharmacol., 54: 397 (1975).CrossRefGoogle Scholar
  30. 30.
    M. A. Wasserman, D. W. Du Charme, R. L. Griffin, G. L. De Graaf and F. G. Robinson, Bronchopulmonary and cardiovascular effects of prostaglandin D2 in the dog. Prostaglandins, 13: 255 (1977).PubMedGoogle Scholar
  31. 31.
    M. Hamberg, P. Hedqvist, K. Strandberg, J. Svensson and B. Samuelsson, Prostaglandin endoperoxides IV Effects on smooth muscle. Life Sci., 16: 451 (1975).PubMedCrossRefGoogle Scholar
  32. 32.
    H. O. J. Collier and P. J. Gardiner, Pharmacology of airways smooth muscle. In: “Evaluation of Bronchodilator Drugs”, D. M. Burley, S. W. Clarke, M. F. Cuthbert, J. W. Paterson and J. H. Shelley, eds., Trust Education and Research in Therapeutics. London (1974).Google Scholar
  33. 33.
    P. J. Gardiner, The effects of some natural prostaglandins on isolated human circular bronchial muscle. Prostaglandins, 10: 607 (1975).PubMedGoogle Scholar
  34. 34.
    K. Strandberg and P. Hedqvist, Bronchial effects of some prostaglandin E & F analogues. Acta. Physiol. Scand., 100: 172 (1977).CrossRefGoogle Scholar
  35. 35.
    P. Hedqvist, K. Strandberg and M. Ramberg, Bronchial and cardiovascular actions of prostaglandin endoperoxides and an endoperoxide analogue. Acta. Physiol. Scand., 103: 299 (1978).PubMedCrossRefGoogle Scholar
  36. 36.
    K. R. Patel, Effect of prostaglandin F2 on lung mechanics in intrinsic asthma. Postgrad. Med. J., 52: 275 (1976).PubMedCrossRefGoogle Scholar
  37. 37.
    A. Szczeklik, R. J. Gryglewski and G. Grerniawska-Mysik, Participation of prostaglandins in pathogenesis of aspirin-sensitive asthma. Naunyn-Schmiedebergs’ Arch. Pharmacol., 297: 599 (1977).CrossRefGoogle Scholar
  38. 38.
    J. Orehek, P. Gayrard, C. Grimaud and J. Charpin, Bronchial reactivity to inhaled prostaglandin F2a in patients with common or aspirin-sensitive asthma. J. Allergy Clin. Immunol., 59: 414 (1977).PubMedCrossRefGoogle Scholar
  39. 39.
    A. A. Mathe and P. Hedqvist, Effect of prostaglandin F2a and E2 on airways conductance in healthy subjects and asthmatic patients. Am. Rev. Resp. Dis., 111: 313 (1975).PubMedGoogle Scholar
  40. 40.
    M. Pasargiklian, S. Bianco and L. Allegra, Clinical, functional and pathogenetic aspects of bronchial reactivity to prostaglandins F2a, El & E2. In: “Adv. Prostaglandin & Thromboxane Res. B. Samuelsson & R. Paoletti, eds., 1:461, Raven Press (1976).Google Scholar
  41. 41.
    J. L. Walker, The regulatory role of prostaglandins in the release of histamine and SRS-A from passively sensitised human lung tissue. In: “Advances in the Biosciences”, S. Bergstrom, and S. Bernhard, eds.Google Scholar
  42. 42.
    J. Iravani and G. N. Melville, Mucociliary activity in the respiratory tract as influenced by prostaglandin El. Respiration, 32: 305 (1975).PubMedCrossRefGoogle Scholar
  43. 43.
    J. Irvani, G. N. Melville and H. G. Richter, Mucus production influenced by drugs: An electron microscope study. Pneumonologic Suppl., 267 (1976).Google Scholar
  44. 44.
    H. J. Biersak, J. R. Hedde, R. Felix and C. Winkler, Mukoziliare Clearance under Prostaglandin El Inhalation. Prax. Pneumol., 32: 105 (1978).Google Scholar
  45. 45.
    S. Bianco, M. Robuschi, R. Cesarani and C. Gandolfi, Prevention of aspecifically induced bronchoconstriction by prostacyclin (PGI2) in asthmatic subjects. IRCS Med. Science. Clin. Med; Clin. Pharmacol. & Ther.; Resp. Sys., 6: 256 (1978).Google Scholar
  46. 46.
    A. Szczeklik, R. J. Gryglewski, E. Nizankowska, R. Nizankowski and J. Musial, Pulmonary and anti-platelet effects of intravenous and inhaled prostacyclin in man. Prostaglandins, 16: 651 (1978).Google Scholar
  47. 47.
    M. Pasargiklian and S. Bianco, Ventilatory and cardiovascular effects of P1 and 6-keto-PGFla by inhalation. Fourth International Prostaglandin Conference (in press) (1979).Google Scholar
  48. 48.
    P. Hamosh and T. Da Silva, The effect of prostaglandin F2ß on expiratory flow rates. Prostaglandins, 10: 599 (1975).PubMedGoogle Scholar
  49. 49.
    P. J. Piper, Release of catecholamine and other substances by antigen and mediators of the anaphylactic reaction. PhD thesis. University of London (1969).Google Scholar
  50. 50.
    H. O. J. Collier and W. J. F. Sweatman, Antagonism by fenamates of prostaglandin F2a and of slow reacting substance on human bronchial muscle. Nature, 219: 864 (1968).CrossRefGoogle Scholar
  51. 51.
    J. Orehek, J. S. Douglas, A. J. Lewis and A. Bouhuys, Prostaglandin regulation of airway smooth muscle tone. Nature, 245: 84 (1973).Google Scholar
  52. 52.
    E. L. Tolman and R. Partridge, Multiple sites of interaction with prostaglandins and non-steroidal anti-inflammatory agents. Prostaglandins, 9: 349 (1975).PubMedGoogle Scholar
  53. 53.
    C. Brink, C. Grimaud, C. Guillot and J. Orehek, The interaction between indomethacin and contractile agents on isolated human airway smooth muscle. Brit. J. Pharmacol. (in press) (1979/80).Google Scholar
  54. 54.
    P. J. Gardiner, J. L. Copas, R. D. Elliot and H. O. J. Collier, Tracheobronchial irritancy of inhaled prostaglandins in the conscious cat. Prostaglandins, 15: 303 (1978).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • M. F. Cuthbert
    • 1
    • 2
  • P. J. Gardiner
    • 3
  1. 1.Department of Pharmacology and TherapeuticsLondon Hospital Medical CollegeLondonUK
  2. 2.Chest Unit, Department of MedicineKings College HospitalLondonEngland
  3. 3.Research DepartmentMiles Laboratories LimitedSlough, BerksEngland

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