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Vasoconstriction and bronchoconstriction induced by 2,5-Di(tert-butyl)1,4-benzohydroquinone, an endoplasmic reticular Ca2+-ATPase inhibitor in isolated and perfused rat lung

  • Allergy, Histamine and Kinins
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Abstract

The microsomal Ca2+-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) induced bronchoconstriction and vasoconstriction in the isolated perfused and ventilated rat lung. These effects were accompanied by increased levels of thromboxane and prostacyclin in the effluent perfusate. The effect of tBuBHQ was inhibited by L-655,240, a thromboxane receptor antagonist, indicating thromboxane-A2-mediated bronchoconstriction and vasoconstriction. Accordingly, the cyclooxygenase inhibitor indomethacin largely blocked the effects of tBuBHQ. The involvement of a phospholipase in the generation of thromboxane A2 (TXA2) was supported by dibucaine protection on tBuBHQ effects. The results from this study indicate that tBuBHQ, probably by inhibiting the microsomal Ca2+-ATPase, can trigger the arachidonic acid cascade leading to the formation of TXA2, which in turn causes bronchoconstriction and vasoconstriction in rat lung.

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References

  1. P. J. Barnes, K. F. Chung and C. P. Page,Inflammatory mediators and asthma. Pharmacol. Rev.40, 49–84 (1988).

    PubMed  Google Scholar 

  2. S. I. Said and H. D. Foda,Pharmacological modulation of lung injury. Am. Rev. Respir. Dis.139, 1553–1564 (1989).

    PubMed  Google Scholar 

  3. R. H. Demling,Role of prostaglandins in acute pulmonary microvascular injury. Ann. N.Y. Acad. Sci.384, 517–534 (1982).

    PubMed  Google Scholar 

  4. W. D. Watkins, P. C. Huttemeier, D. Kong and M. B. Peterson,Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: Effect of an imidazole derivative. Prostaglandins23, 273–285 (1982).

    PubMed  Google Scholar 

  5. B. Samuelsson,Leukotrienes: Mediators of immediate hypersensitivity reactions and inflammation. Science220, 568–576 (1983).

    PubMed  Google Scholar 

  6. D. F. Rogers, S. Dijk and P. J. Barnes,Bradykinin-induced plasma exudation in guinea-pig airways: Involvement of platelet activating factor. Br. J. Pharmacol.101, 739–735 (1990).

    PubMed  Google Scholar 

  7. J. Frölich, M. Ogletree and K. Brigham,Gram-negative endotoxemia in sheep: Pulmonary hypertension correlated to pulmonary thromboxane synthesis. Adv. Prostaglandin Thromboxane Res.7, 745 (1980).

    PubMed  Google Scholar 

  8. G. H. Gurtner, A. Knoblauch, P. L. Smith, H. Sies and N. F. Adkinson,Oxidant-and lipid-induced pulmonary vasoconstriction mediated by arachidonic acid metabolites. J. Appl. Physiol.55, 949–954 (1983).

    PubMed  Google Scholar 

  9. I. S. Farrukh, A. M. Sciuto, E. Spannhake, G. H. Gurtner and J. R. Michael,Leukotriene D 4 increases pulmonary vascular permeability and pressure by different mechanisms in the rabbit. Am. Rev. Respir. Dis.134, 229–232 (1986).

    PubMed  Google Scholar 

  10. K. Olafsdottir, L. Atzori, A. Ryrfeldt, M. Berggren, M. Kumlin and P. Moldéus,Mechanisms of hydroperoxide-induced broncho-and vasoconstriction in isolated and perfused rat lung. Pharmacol. Toxicol.68, 181–186 (1991).

    PubMed  Google Scholar 

  11. R. J. Flower and G. J. Blackwell,The importance of phospholipase-A 2 in prostaglandin biosynthesis. Biochem. Pharmacol.25, 285–291 (1976).

    PubMed  Google Scholar 

  12. R. Burgoyne and A. Morgan,The control of free arachidonmic acid levels. Trends Biol. Sci.15, 365–366 (1990).

    Google Scholar 

  13. S. Rittenhouse-Simmons and D. Deykin,The mobilization of arachidonic acid in platelets, exposed to thrombin or ionophore A23187. J. Clin. Invest.60, 495–498 (1977).

    PubMed  Google Scholar 

  14. E. Carafoli,Intracellular calcium homeostasis. Ann. Rev. Biochem.56, 395–433 (1987).

    PubMed  Google Scholar 

  15. G. A. Moore, D. J. McConkey, G. E. N. Kass, P. J. O'Brien and S. Orrenius,2,5-Di(tert-butyl)-1,4-benzohydroquinone — a novel inhibitor of liver microsomal Ca 2+ sequestration. FEBS Lett.224, 331–336 (1987).

    PubMed  Google Scholar 

  16. G. E. N. Kass, S. Duddy, G. A. Moore and S. Orrenius,2,5-Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca 2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca 2+-pool. J. Biol. Chem.264, 15192–15198 (1989).

    PubMed  Google Scholar 

  17. S. K. Duddy, G. E. N. Kass and S. Orrenius,Ca 2+-mobilizing hormones stimulate Ca 2+ efflux from hepatocytes. J. Biol. Chem.264, 20863–20866 (1989).

    PubMed  Google Scholar 

  18. J. Llopis, G. E. N. Kass, S. K. Duddy, G. C. Farrell, A. Gahm and S. Orrenius,Mobilization of the hormonesensitive calcium pool increases hepatocyte tight junctional permeability in the perfused rat liver. FEBS Lett.280, 84–86 (1991).

    PubMed  Google Scholar 

  19. Å. Ryrfeldt and E. NilssonLung uptake and antianaphylactic effects of WD 2131 (a β-adrenergic agonist) in perfused guinea-pig lungs. Acta Pharmacol. Toxicol.48, 390–396 (1981).

    Google Scholar 

  20. M. O. Amdur and J. Mead,Mechanisms of respiration in unanesthetized guinea pigs. Am. J. Physiol.192, 364–368 (1958).

    PubMed  Google Scholar 

  21. J. Waldeck,En mätmetod för att undersöka läkemedels effekter på luftvägarna. Thesis, Lunds Technical University (1987).

  22. G. Scherphof and H. Westenberg,Stimulation and inhibition of pancreatic phospholipase A 2 by local anaesthetics as a result of their interaction with the substrate. Biochim. Biophys. Acta398, 442–451 (1975).

    PubMed  Google Scholar 

  23. J. Svensson, K. Strandberg, T. Tuvemo and M. Hamberg,Thromboxane A 2:Effects on airway and vascular smooth muscle. Prostaglandins14, 425–436 (1977).

    PubMed  Google Scholar 

  24. I. S. Farrukh, J. R. Michael, S. P. Peters, A. M. Sciuto, N. F. Adkinson, H. S. Freeland, A. Paky, E. W. Spannhake, W. R. Summer and G.H. Gurtner,The role of cyclooxygenase and lipoxygenase mediators in oxidant-induced lung injury. Am. Rev. Respir. Dis.137, 1343–1349 (1988).

    PubMed  Google Scholar 

  25. P. B. Zanaboni, J. D. Bradley, L. J. Baudendistel, R. O. Webster and T. E. Dahms,Cyclooxygenase inhibition prevents PMA-induced increases in lung vascular permeability. J. Appl. Physiol.69, 1494–1501 (1990).

    PubMed  Google Scholar 

  26. L. Atzori, K. Olafsdottir, A. M. Corriga, G. Bannenberg, Å. Ryrfeldt and P. Moldèus,Thiol modifications in H 2 O 2 and thromboxane induced vaso-and bronchoconstriction in rat perfused lung. J. Appl. Physiol.71, 1309–1314 (1991).

    PubMed  Google Scholar 

  27. I. W. Rodger,Excitation-contraction coupling and uncoupling in airway smooth muscle. Br. J. Pharmacol.20, 255S-265S (1985).

    Google Scholar 

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Authors and Affiliations

  1. Department of Toxicology and Institute of Environmental Medicine, Karolinska Institutet, Box 60400, S-10401, Stockholm, Sweden

    L. Atzori, G. Bannenberg, A. M. Corriga, Å Ryrfeldt & P. Moldeus

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  1. L. Atzori
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  2. G. Bannenberg
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  3. A. M. Corriga
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  4. Å Ryrfeldt
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  5. P. Moldeus
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Atzori, L., Bannenberg, G., Corriga, A.M. et al. Vasoconstriction and bronchoconstriction induced by 2,5-Di(tert-butyl)1,4-benzohydroquinone, an endoplasmic reticular Ca2+-ATPase inhibitor in isolated and perfused rat lung. Agents and Actions 36, 33–38 (1992). https://doi.org/10.1007/BF01991225

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  • DOI: https://doi.org/10.1007/BF01991225

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