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Inflammation Research

, Volume 45, Issue 12, pp 583–589 | Cite as

Effects of three different Ca2+-ATPase inhibitors on Ca2+ response and leukotriene release in RBL-2H3 cells

  • R. Akasaka
  • R. Teshima
  • H. Ikebuchi
  • J. Sawada
Original Research Papers

Abstract

The effects of three Ca2+-ATPase inhibitors, thapsigargin (TG), cyclopiazonic acid (CPA), and 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), on the Ca2+ response, degranulation, and leukotriene C4 (LTC4) release in RBL-2H3 cells were investigated. All three compounds elevated the intracellular free Ca2+ concentration ([Ca2+]i), and caused degranulation in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator. The dose-dependency of each compound in the Ca2+ response was in good agreement with that in degranulation. TG and CPA also caused the release of LTC4 in a dose-dependent manner, and this effect was unaffected by TPA or calphostin C, a selective PKC inhibitor. DTBHQ, however, did not induce LTC4 release, and rather inhibited the antigen-induced release of LTC4. These results suggest [1] that both degranulation and LTC4 release caused by these compounds are dependent on their [Ca2+]i increasing effect, [2] that degranulation and LTC4 release are mediated via independent pathways following the Ca2+ response, and [3] that DTBHQ additionally prevents the synthesis of LTC4 possibly by inhibition of 5-lipoxygenase.

Key words

Basophilic leukemia cell Ca2+-ATPase inhibitor Cytosolic calcium level Degranulation Leukotriene C4 release 

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References

  1. [1]
    Lewis RA, Austen KF. Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds. Nature 1981;293:103–8.CrossRefPubMedGoogle Scholar
  2. [2]
    Beaven MA, Moore JP, Smith GA, Hesketh TR, Metcalf JC. The calcium signal and phosphatidylinositol breakdown in 2H3 cells. J Biol Chem 1984;259:7137–42.PubMedGoogle Scholar
  3. [3]
    Maeyama K, Hohman RJ, Ali H, Cunha-Melo JR, Beaven MA. Assessment of IgE-receptor function through measurement of hydrolysis of membrane inositol phospholipids. J Immunol 1988;140:3919–27.PubMedGoogle Scholar
  4. [4]
    Kass GEN, Duddy SK, Moore GA, Orrenius S. 2,5-Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. J Biol Chem 1989;264:15192–8.PubMedGoogle Scholar
  5. [5]
    Akasaka R, Teshima R, Kitajima S, Momma J, Inoue T, Kurokawa Y, et al. Effects of hydroquinone-type and phenolic antioxidants on calcium signals and degranulation of RBL-2H3 cells. Biochem Pharmacol 1996;51:1513–9.CrossRefPubMedGoogle Scholar
  6. [6]
    Thastrup O. Role of Ca2+-ATPase in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2+-ATPase inhibitor, thapsigargin. Agents Actions 1990;29:8–15.CrossRefPubMedGoogle Scholar
  7. [7]
    Thastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc Natl Acad Sci USA 1990;87:2466–70.PubMedGoogle Scholar
  8. [8]
    Seidler NW, Jona I, Vegh M, Martonosi A. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem 1989;264:17816–23.PubMedGoogle Scholar
  9. [9]
    Demaurex N, Lew DP, Krause KH. Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. J Biol Chem 1992;267:2318–24.PubMedGoogle Scholar
  10. [10]
    Horikoshi Y, Furuno T, Teshima R, Sawada J, Nakanishi M. Thapsigargin-induced nuclear signals in rat basophilic leukaemia cells. Biochem J 1994;304:57–60.PubMedGoogle Scholar
  11. [11]
    Falcone D, Fewtrell C. Ca2+-ATPase inhibitor, cyclopiazonic acid, releases Ca2+ from intracellular stores in RBL-2H3 mast cells and activates a Ca2+ influx pathway that is permeable to sodium and manganese. J Cell Physiol 1995;164:205–13.PubMedGoogle Scholar
  12. [12]
    Teshima R, Ikebuchi H, Sawada J, Furuno T, Nakanishi M, Terao T. Effects of herbimycin A and ST638 on Fcε receptor-mediated histamine release and Ca2+ signals in rat basophilic leukemia (RBL-2H3) cells. Biochim Biophys Acta 1994;1221:37–46.PubMedGoogle Scholar
  13. [13]
    Barusumian EL, Iserskey C, Petrino MG, Siraganian RP. IgE-induced histamine release from rat basophilic leukemia cell lines: isolation of releasing and nonreleasing clones. Eur J Immunol 1981;11:317–23.Google Scholar
  14. [14]
    Teshima R, Ikebuchi H, Terao T, Nakanishi M. The effect of staurosporine on Ca2+ signals in rat basophilic leukemia (RBL-2H3) cells. Chem Pharm Bull 1991;39:747–51.PubMedGoogle Scholar
  15. [15]
    Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 1985;260:3440–50.PubMedGoogle Scholar
  16. [16]
    Igarashi Y, Lundgren JD, Shelhamer JH, Kaliner MA, White MV. Effects of inhibitors of arachidonic acid metabolism on serotonin release from rat basophilic leukemia cells. Immunopharmacology 1993;25:131–44.CrossRefPubMedGoogle Scholar
  17. [17]
    Schwartz LB, Lewis RA, Seldin D, Austen KF. Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. J Immunol 1981;126:1290–4.PubMedGoogle Scholar
  18. [18]
    Hirasawa N, Santini F, Beaven MA. Activation of the mitogen-activated protein kinase/cytosolic phoshosipase A2 pathway in rat mast cell line. Indications of different pathways for release of arachidonic acid and secretory granules. J Immunol 1995;154:5391–402.PubMedGoogle Scholar
  19. [19]
    van Haaster CMCJ, Engels W, Lemmens PJMR, Hornstra G, van der Vusse GJ, Heemskerk JWM. Differential release of histamine and prostagrandin D2 in rat peritoneal mast cells: roles of cytosolic calcium and protein tyrosine kinases. Biochim Biophys Acta 1995;1265:79–88.PubMedGoogle Scholar
  20. [20]
    Amon U, von Stebut E, von Gizycki U, Wolff HH. Control function of protein kinase C isozymes on leukotriene generation from human basophils? Agents Actions 1994;41:C9–10.CrossRefGoogle Scholar
  21. [21]
    Rosenthal MD, Franson RC. Separation of agonist-stimulated arachidonate mobilization from subsequent leukotriene B4 synthesis in human neutrophils: Different effects of oleoylacetylglycerol and phorbol myristate acetate as priming agents. J Cell Physiol 1994;160:522–30.PubMedGoogle Scholar
  22. [22]
    McColl SR, Hurst NP, Cleland LG. Modulation by phorbol myristate acetate of arachidonic acid release and leukotriene synthesis by human polymorphonuclear leukocytes stimulated with A23187. Biochem Biophys Res Commun 1986;141:399–404.CrossRefPubMedGoogle Scholar
  23. [23]
    Levine L. Inhibition of the A-23187-stimulated leukotriene and prostaglandin biosynthesis of rat basophil leukemia (RBL-1) cells by non-steroidal anti-inflammatory drugs, antioxidants, and calcium channel blockers. Biochem Pharmacol 1983;32:3023–6.PubMedGoogle Scholar
  24. [24]
    Murakami M, Austen KF, Arm JP. Cytokine regulation of arachidonic acid metabolism in mast cells. In: Kitamura Y, Yamamoto S, Galli SJ, Greaves MW, editors. Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function. New York: Raven Press, 1995:25–37.Google Scholar
  25. [25]
    Ford-Hutchinson AW, Gresser M, Young RN. 5-Lipoxygenase. Annu Rev Biochem 1994;63:383–417.CrossRefPubMedGoogle Scholar
  26. [26]
    Laursen LS, Naesdal J, Bukhave K, Lauritsen K, Rask-Madsen J. Selective 5-lipoxygenase inhibition in ulcerative colitis. Lancet 1990;335:683–5.PubMedGoogle Scholar
  27. [27]
    Lau CK, Bélanger PC, Dufresne C, Scheigetz J, Therien M, Fitzsimmons B, et al. Development of 2,3-dihydro-6-(3-phenoxypropyl)-2-(2-phenylethyl)-5-benzofuranol (L-670, 630) as a potent and orally active inhibitor of 5-lipoxygenase. J Med Chem 1992;35:1299–318.CrossRefPubMedGoogle Scholar
  28. [28]
    Kikuchi M, Hashimura Y, Tsuzurahara K, Nagasawa M, Inoue H, Taniguchi T, et al. 4-Acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and inhibitory effect on 5-lipoxygenase and leucotriene B4 production. Biol Pharm Bull 1994;17:1038–46.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1996

Authors and Affiliations

  • R. Akasaka
    • 1
  • R. Teshima
    • 1
  • H. Ikebuchi
    • 1
  • J. Sawada
    • 1
  1. 1.Division of Biochemistry and ImmunochemistryNational Institute of Health SciencesTokyoJapan

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