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, Volume 21, Issue 1–2, pp 32–37 | Cite as

Oxatomide inhibits the release of bronchoconstrictor arachidonic acid metabolites (iLTC4 and PGD2) from rat mast cells and guinea-pig lung

  • Y. Kosaka
  • H. Kawabe
  • A. Ishii
Histamine and Kinins

Abstract

The effect of oxatomide, an orally active antiallergic drug, on immunoreactive LTC4 (iLTC4) production has been studied in rat peritoneal exudate cells (PEC) and guinea-pig lung fragments using the calcium ionophore A23187 and specific antigen in vitro. Oxatomide (10−5M) inhibited iLTC4 release by 70% with A23187 from rat PEC, and by 48% with antigen from guinea-pig lung. Oxatomide is supposed to affect the biosynthesis pathway of leukotrienes, because oxatomide inhibits 5-lipoxygenase from guinea-pig peritoneal leukocytes with an IC50 17 μM. Oxatomide also depressed the release of PGD2 from rat peritoneal mast cells stimulated by A23187 (IC50 4.2 μM). The effects of oxatomide on iLTC4 and PGD2 release were more potent than other antiallergic drugs (DSCG, ketotifen, tranilast).

Keywords

Mast Cell Arachidonic Acid A23187 Calcium Ionophore Ketotifen 
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. [1]
    S. E. Dahlén, P. Hedqvist, S. Hammarström and B. Samuelsson,Leukotrienes are Potent Constrictors of Human Bronch. Nature (London)288, 484–486 (1980).Google Scholar
  2. [2]
    C. J. Hanna, M. K. Bach, P. D. Pare and R. P. Schelleberg,Slow-reacting Substance (Leukotriens) Contract Human Airway and Pulmonary Vascular Smooth Muscle in vitro. Nature (London)290, 343–344 (1981).Google Scholar
  3. [3]
    T. R. Jones, C. Davis and E. E. Daniel,Pharmacological Study of the Contractile Activity of Leukotriene C 4 and D 4 on Isolated Human Airway Smooth Muscle. Can. J. Physiol. Pharmacol.60, 638–643 (1982).Google Scholar
  4. [4]
    J. F. Burka and M. H. Saad,Mediators of Arachidonic Acid-induced Contractions of Indomethacin-treated Guinea-pig Airways: Leukotriens C 4 and D 4. Br. J. Pharmacol.81, 465–473 (1984).Google Scholar
  5. [5]
    M. K. Bach and J. R. Brashler,Ionophore A23187-induced Production of Slow Reacting Substance of Anaphylaxis (SRS-A) by Rat Peritoneal Cells in vitro: Evidence for Production by Mononuclear Cells. J. Immunol.120, 998–1005 (1978).Google Scholar
  6. [6]
    N. Chakravarty,Effect of Arachidonic Acid Metabolism on the Release of Histamine and SRS (Leukotriens) from Guinea-pig Lung. Agents and Actions14, 429–434 (1984).Google Scholar
  7. [7]
    M. Ennis, S. E. Barrow and I. A. Blair,Prostaglandin and Histamine Release from Stimulated Rat Peritoneal Mast Cells. Agents and Actions14, 397–400 (1984).Google Scholar
  8. [8]
    S. T. Holgate, G. B. Burns, C. Robinson and M. K. Church,Anaphylactic- and Calcium-dependent Generation of Prostaglandin D 2 (PGD 2),Thromboxane B 2 and Other Cyclooxygenase Products of Arachidonic Acid by Dispersed Human Lung Cells and Relationship to Histamine Release. J. Immunol.133, 2138–2144 (1984).Google Scholar
  9. [9]
    L. J. Roberts II, R. A. Lelwis, J. A. Oates and K. F. Austem,Prostaglandin, Thromboxane and 12-hydroxy-5.8.10.14-eicosatetraenoic acid Production by Ionophore-stimulated Rat Serosal Mast Cells. Biochim. Biophys. Acta575, 185–192 (1979).Google Scholar
  10. [10]
    E. S. Schulman, H. H. Newball, L. M. Demers, F. A. Fitzpatrick and N. F. Adkinson Jr.,Anaphylactic Release of Thromboxane A 2,Prostaglandin D 2 and Prostacyclin from Human Lung Parenchyma. Am. Res. Respir. Dis.124, 402–406 (1981).Google Scholar
  11. [11]
    M. A. Wasserman, R. L. Griffin and F. B. Marsalisi,Potent Bronchoconstrictor Effects of Aerosolized Prostaglandin D 2 in Dogs. Prostaglandins20, 704–715 (1980).Google Scholar
  12. [12]
    C. A. Gruetter, D. B. McNamara, A. L. Hyman and P. J. Kadowitz,Contractile Effects of a PGH 2 Analog and PGD 2 on Intrapulmonary Vessels. Am. J. Physiol.234, H139–145 (1978).Google Scholar
  13. [13]
    J. Svensson, K. Strandberg, T. Tuvemo and M. Hamberg,Thromboxane A 2:Effects of Airway and Vascular Smooth Muscle. Prostaglandins14, 425–436 (1977).Google Scholar
  14. [14]
    F. Awouters, C. J. E. Niemegeers, J. van den Berk, J. M. van Nueten, F. M. Lenaerts, M. Borgers, K. H. L. Schellekens, A. Broeckaert, J. De Cree and P. A. J. Janssen,Oxatomide, A New Orally Active Drug which Inhibits both the Release and the Effects of Allergic Mediators. Experientia33, 1657–1659 (1977).Google Scholar
  15. [15]
    K. Ohmori, H. Ishii, K. Shuto and N. Nakamizo,Pharmacological Studies on Oxatomide: (4) Effect on the Histamine Release from Rat Isolated Peritoneal Exudate Cells (PEC) and Lung Slices. Folia pharmacol. japon.80, 441–449 (1982).Google Scholar
  16. [16]
    K. Ohmori, H. Ishii, T. Kubota, K. Shuto and N. Nakamizo,Inhibitory Effects of Oxatomide on Several Activities of SRS-S and Synthetic Leukotriens in Guinea-pigs and Rats. Arch. Int. Pharmacodyn. Therap.275, 139–150 (1985).Google Scholar
  17. [17]
    U. Martin and D. Romer,The Pharmacological Properties of a New, orally Active Antianaphylatic Compound: Ketotifen, a Benzocycloheptathiophene. Arzneim.-Forsh.28, 770–782 (1978).Google Scholar
  18. [18]
    P. Sheard and A. M. J. N. Blair,Disodium Cromoglycate, Activity in three in vitro Models of the Immediate Hypersensitivity Reaction in Lung. Int. Archs. Allergy Appl. Immunol.38, 217–224 (1970).Google Scholar
  19. [19]
    M. Nakazawa, T. Yoshimura, J. Naito and H. Azuma,Pharmacological Properties of N-(3′,4′-dimethoxycinnamoyl)anthranilic acid(N-5′), a New Anti-otopic Agent(5)-Influence of N-5′ on the Histamine Release from Peritoneal Exudate Cells. Folia pharmacol. japon.74, 483–490 (1974).Google Scholar
  20. [20]
    T. J. Sullivan, K. L. Parker, W. Stenson and C. W. Parker,Modulation of Cyclic AMP in Purified Rat Mast Cells I. Responses to Pharmacologic, Metabolic, and Physical Stimuli. J. Immunol.114, 1473–1479 (1975).Google Scholar
  21. [21]
    K. Ohmori, H. Ishii, Y. Takei, K. Shuto and N. Nakamizo,Pharmacological Studies on Oxatomide: (3) Effect on Experimental Asthma and Shultz-Dale Response in Rats and Guinea pigs. Folia pharmacol. japon.80, 481–493 (1982).Google Scholar
  22. [22]
    K. Ohmori, H. Ishii, T. Hirayama, K. Shuto and N. Nakamizo,Pharmacological Studies on Oxatomide (KW-4354): (1) Effect on Passive Cutaneous Anaphylaxis (PCA) in Rats and Guiena pigs. Folia pharmacol. japon.80, 251–260 (1982).Google Scholar
  23. [23]
    S. Narumiya, T. Ogorochi, K. Nakao and O. Hayaishi,Prostaglandin D 2 in Rat Brain, Spinal Cord and Pituitary: Basal Level and Regional Distribution. Life Sci.31, 2093–2103 (1982).Google Scholar
  24. [24]
    S. Watanabe Kohno and C. W. Parker,Role of Arachidonic Acid in the Biosynthesis of Slow Reacting Substance of Anaphylaxis (SRS-A) from sensitized Guinea-pig Lung Fragments: Evidence that SRS-A is very Similar of Identical Structurally to Nonimmunologically Induced Forms of SRS. J. Immunol.125, 946–955 (1980).Google Scholar
  25. [25]
    K. Ochi, T. Yoshimoto and S. Yamamoto,Arachidonate 5-Lipoxygenase of Guinea Pig Peitoneal Polymorphonuclear Leukocytes. J. Biol. Chem.258, 5754–5758 (1983).Google Scholar
  26. [26]
    E. C. Ku, J. M. Wasvary and W. D. Cash,Diclofenac sodium (GP45840, Voltaren), A potent Inhibitor of Prostaglandin Synthetase. Biochem. Pharmacol.24, 641–643 (1975).Google Scholar
  27. [27]
    M. Kishimoto, S. Torii, M. Yamada, T. Hida and M. Katagiri,Effect of Oxatomide (KW-4354) on SRS in Human PMN. Allery no Rinshyo (Japan)4, 655–657 (1984).Google Scholar
  28. [28]
    H. Komatu, A. Ujiie and J. Naito,Effect of Tranilast on the Release of Slow Reacting Substance of Anaphylaxis (SRSA) and on its Contraction of Smooth Muscle. Folia pharmacol. japon.82, 47–55 (1983).Google Scholar
  29. [29]
    H. Tomioka, S. Yoshida, M. Tanaka and A. Kumagai,Inhibition of Chemical Mediator Release from Human Leukocytes by a New Antihistamine Drug, HC20-511 (Ketotifen). Monogr. Allergy14, 313–317 (1979).Google Scholar
  30. [30]
    D. J. Heavey, P. Lumley, S. E. Barrow, M. B. Murphy, P. P. A. Humphrey and C. T. Dollery,Effects of Intravenous Infusions of Prostaglandin D 2 in Man. Prostaglandins28, 755–767 (1984).Google Scholar
  31. [31]
    F. J. Persico and K. Carpenter,The Influence of Oxatomide on Calcium Levels in Rat Mast Cells. Abstract Am. Soc. Pharmacol. Exp. Ther. meeting, Portland, OR, August 19–23 (1979).Google Scholar
  32. [32]
    R. J. Flower and J. R. Vane,Inhibition of Prostaglandin Biosynthesis. Biochem. Pharmac.23, 1439–1450 (1974).Google Scholar

Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • Y. Kosaka
    • 1
  • H. Kawabe
    • 1
  • A. Ishii
    • 1
  1. 1.Pharmaceutical Research LaboratoriesKyowa Hakko Kogyo Co. Ltd.Shizuoka-kenJapan

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