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Mechanism of leukotriene-induced contraction of isolated guinea pig tracheal smooth muscle

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Abstract

The mechanical response of guinea pig tracheal smooth muscle to leukotriene (LT) B4, C4, D4 and E4 was investigated, and the effects of several agents on LT-induced contraction were determined. Agents used in the present study were: verapamil, a Ca-channel blocker; dibutyryl cyclic-AMP (DBcAMP); aminophylline; N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), a calmodulin antagonist; N-(6-aminohexyl)-1-naphthalene-sulfonamide hydrochloride (W-5), resembling W-7 in structure but without calmodulin antagonism. The results were as follows: 1) LTB4 had a contractile activity, dependent on the [Ca]o concentration; it was suppressed by a [Mg]o increase to 1.2 mM and over. Little effect was observed from other drugs. 2) Contractile activities of LTC4, D4 and E4 were dose-dependent, depending upon [Ca]o as well as LTB4. 3) Verapamil (5×10−6−10−3 M), DBcAMP (3×10−6−3×10−3 M) and aminophylline (3×10−8−3×10−3 M) suppressed LTs (C4, D4, and E4, 10−8 M)-induced contraction dose-dependently. However, W-7 and W-5 did not suppress LT-induced contraction. These results suggest that the LTC4-, D4-and E4-induced responses could be explained by the effect of LTC4, D4 and E4 on increasing Ca influx through the plasma membrane.

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References

  1. Altura BM, Altura BT (1981) Magnesium ions and contraction of vascular smooth muscles: relationship to some vascular diseases. Fed Proc 40:2672–2677

    PubMed  CAS  Google Scholar 

  2. Asano M, Suzuki Y, Hidaka H (1982) Effects of various calmodulin antagonists on contraction of rabbit aortic strips. J Pharmacol Exp Ther 220:191–195

    PubMed  CAS  Google Scholar 

  3. Blackmore PF, El-Refai MF, Exton JH (1979) α-Adrenergic blockade and inhibition of A23187 mediated Ca2+ uptake by the calcium antagonist verapamil in rat liver cells. Mol Pharmacol 15:598–606

    PubMed  CAS  Google Scholar 

  4. Borgeat P, Samuelsson B (1979) Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem 254:7865–7869

    PubMed  CAS  Google Scholar 

  5. Bray MA, Ford-Hutchinson AW, Smith MJH (1981) Leukotriene B4: an inflammatory mediator in vivo. Prostaglandins 22:213–222

    Article  PubMed  CAS  Google Scholar 

  6. Brocklehurst WE (1960) The release of histamine and formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol (Lond) 151:416–435

    CAS  Google Scholar 

  7. Brocklehurst WE (1981) “Steps in the dark” — An outline history of the study of SRS-A. In: SRS-A and leukotrienes. Research Studies Press, Chichester, p 7

    Google Scholar 

  8. Bulbring E, Tomita T (1970) Effects of Ca removal on the smooth muscle of the guinea-pig taenia coli. J Physiol (Lond) 210:217–232

    CAS  Google Scholar 

  9. Epstein PM, Fiss K, Hachisu R, Andrenyak DM (1982) Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulin. Biochem Biophys Res Commun 105:1142–1149

    Article  PubMed  CAS  Google Scholar 

  10. Fanta CH, Vanugopalan CS, Lacouture PG, Drazen JM (1982) Inhibition of bronchoconstriction in the guinea pig by a calcium channel blocker, Nifedipine. Am Rev Respir Dis 125:61–65

    PubMed  CAS  Google Scholar 

  11. Feldberg W, Kellaway CH (1938) Liberation of histamine and formation of lysocithin-like substances by cobra venom. J Physiol (Lond) 94:187–226

    CAS  Google Scholar 

  12. Findlay SR, Leary TM, Parker CW, Bloomquist EI, Scheid CR (1982) Contractile events induced by LTD4 and histamine in smooth muscle — a function of Ca2+ utilization. Am J Physiol 243:C133-C138

    PubMed  CAS  Google Scholar 

  13. Ford-Hutchinson AW, Rackham A, Zamboni R, Rokach J, Roy S (1983) Comparative biological activities of synthetic leukotriene B4 and itsω-oxidation products. Prostaglandins 25:29–36

    Article  PubMed  CAS  Google Scholar 

  14. Goodfort PJ (1967) The calcium content of the smooth muscle of the guinea-pig taenia coli. J Physiol (Lond) 192:145–157

    Google Scholar 

  15. Hammarström S (1981) Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver, and kidney. J Biol Chem 256:9573–9578

    PubMed  Google Scholar 

  16. Hanasaki K, Takemoto H, Sugimoto J, Kajimoto N (1979) Influence of magnesium ions on calcium-influx and release of tissue calcium ions in the smooth muscle of isolated guinea-pig vas deferens. Acta Medica Kinki Univ 4:441–446

    CAS  Google Scholar 

  17. Hidaka H, Yamaki T, Asano M, Totsuka T (1978) Involvement of calcium in cyclic nucleotide metabolism in human vascular smooth muscle. Blood Vessels 15:55–64

    PubMed  CAS  Google Scholar 

  18. Hidaka H, Yamaki T, Totsuka T, Asano M (1979) Selective inhibitors of Ca2+-binding modulator of phosphodiesterase produce vascular relaxation and inhibit actin-myosin interaction. Mol Pharmacol 15:49–59

    PubMed  CAS  Google Scholar 

  19. Kawanishi M, Baba K, Tomita T (1984) Effects of Na removal and readmission on the mechanical response in the guinea-pig tracheal smooth muscle. Jpn J Physiol 34:127–139

    PubMed  CAS  Google Scholar 

  20. Kellaway CH, Trethewie ER (1940) The liberation of a slow-reacting smooth muscle stimulating substance in anaphylaxis. Q J Exp Physiol 30:121–145

    CAS  Google Scholar 

  21. Lewis GP (1981) Lipoxygenase-derived metabolites of arachidonate: release and mode of action. Agents Actions 11:569–571

    Article  PubMed  CAS  Google Scholar 

  22. Lewis RA, Austen KF (1981) Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds. Nature 293:103–107

    Article  PubMed  CAS  Google Scholar 

  23. Matsumoto S, Takagi K, Satake T (1983) Effect of allergen inhalation sensitization on pulmonaryβ-adrenergic receptors. Jpn J Allergol 32:221–228

    CAS  Google Scholar 

  24. Meisheri KD, Hwang O, van Breemen C (1981) Evidence for two separate Ca2+ pathways in smooth muscle plasmalemma. J Membr Biol 59:19–25

    Article  PubMed  CAS  Google Scholar 

  25. Morris HR, Taylor GW, Piper PJ, Tippins JR (1980) Structure of slow-reacting substance of anaphylaxis from guinea-pig lung. Nature 285:104–107

    Article  PubMed  CAS  Google Scholar 

  26. Murphy RC, Hammarström S, Samuelsson B (1979) Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci USA 76:4275–4279

    Article  PubMed  CAS  Google Scholar 

  27. Naccache PH, Molski THP, Becker EL, Borgeat P, Picard S, Vallerand P, Shaafi RI (1982) Specificity of the effect of lipoxygenase metabolites of arachidonic acid on calcium homeostasis in neutrophils. J Biol Chem 257:8608–8611

    PubMed  CAS  Google Scholar 

  28. Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220:568–575

    Article  PubMed  CAS  Google Scholar 

  29. Samuelsson B, Hammarström S (1980) Nomenclature for leukotrienes. Prostaglandins 19:645–646

    Article  PubMed  CAS  Google Scholar 

  30. Samuelsson B, Hammarström S (1982) Leukotrienes: a novel group of biologically active compounds. Vitam Horm 39:1–28

    Article  PubMed  CAS  Google Scholar 

  31. Serhan CN, Fridovich J, Goetzl EJ, Dunham PB, Weissmann G (1982) Leukotriene B and phosphatidic acid are calcium ionophores. Studies employing arsenazo III in liposomes. J Biol Chem 257:4746–4752

    PubMed  CAS  Google Scholar 

  32. Silver PJ, DiSalvo J (1979) Adenosine 3′:5′-Monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin. J Biol Chem 254:9951–9957

    PubMed  CAS  Google Scholar 

  33. Sirois P, Borgeat P, Jeanson A, Roy S, Girard G (1980) The action of leukotriene B4 (LTB4) on the lung. Prostaglandins Med 5:429–444

    Article  PubMed  CAS  Google Scholar 

  34. Sirois P, Brousseau Y (1983) Leukotriene transformation by guinea-pig. Prostaglandins Leukotrienes Med 10:133–143

    Article  CAS  Google Scholar 

  35. Ueno A, Tanaka K, Katori M (1982) Possible involvement of thromboxane in bronchoconstrictive and hypertensive effects of LTC4 and LTD4 in guinea pigs. Prostaglandins 23:865–878

    Article  PubMed  CAS  Google Scholar 

  36. Vaghy PL, Johnson JD, Matlib MA, Wang T, Schwartz A (1982) Selective inhibition of Na+-induced Ca2+ release from heart mitochondria by diltiazem and certain other Ca2+ antagonist drugs. J Biol Chem 257:6000–6002

    PubMed  CAS  Google Scholar 

  37. Weichman BM, Muccitelli RM, Osborn RR, Holden DA, Gleason JG, Wasserman MA (1982) In vitro and in vivo mechanisms of leukotriene-mediated bronchoconstriction in the guinea pig. J Pharmacol Exp Ther 222:202–208

    PubMed  CAS  Google Scholar 

  38. Weichman BM, Muccitelli RM, Tucker SS, Wasserman MA (1983) Effect of calcium antagonists on leukotriene D4-induced contractions of the guinea-pig trachea and lung parenchyma. J Pharmacol Exp Ther 225:310–351

    PubMed  CAS  Google Scholar 

  39. Weiss EB, Mullick PC (1983) Leukotriene effect in airways smooth muscle: calcium dependency and verapamil inhibition. Prostaglandins Leukotrienes Med 12:53–66

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Nagoya, Tsuruma, Showa-ku, 466, Nagoya, Japan

    Tomoyasu Sasaki, Kenzo Takagi & Tatsuo Satake

  2. Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Tsuruma, Showa-ku, 466, Nagoya, Japan

    Satoru Sugiyama & Takayuki Ozawa

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  1. Tomoyasu Sasaki
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  2. Kenzo Takagi
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  3. Tatsuo Satake
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  4. Satoru Sugiyama
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  5. Takayuki Ozawa
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Sasaki, T., Takagi, K., Satake, T. et al. Mechanism of leukotriene-induced contraction of isolated guinea pig tracheal smooth muscle. Lung 162, 369–380 (1984). https://doi.org/10.1007/BF02715669

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