, Volume 12, Issue 6, pp 575–584 | Cite as

Stimulation of guinea pig neutrophil superoxide anion-producing system with thymol

  • Yukio Suzuki
  • Hiroaki Furuta
Original Articles


Thymol stimulated O 2 production in guinea pig neutrophils. O 2 production occurred about 30 sec after the addition of thymol, and its rate was independent of extracellular Ca2 +. Thymol-induced activity was inhibited by trifluoperazine (TFP), an inhibitor of protein kinase c, and its IC50 was less than that for 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced activity. After complete activation, O 2 production was reversed by addition of TFP or by washing out and resuspending in a stimuli-free medium. The responsiveness of the thymol-pulsed cells to another stimulus, TPA, was somewhat more than resting cells, but the responsiveness of the former cells to thymol was about half that of the latter cells. The ATP level of cells was reduced to one half its initial value during activation by thymol. These data suggest that the magnitude of thymol-induced O 2 production in neutrophils is dependent on the initial density of the binding sites of the cells with thymol and the initial intracellular ATP concentration.


Public Health Internal Medicine Protein Kinase Superoxide Phorbol 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Harvey, S. C. 1985. Antiseptics and disinfectants.In Goodman and Gilman's The Pharmacological Basis of Therapeutics. L. S. Goodman, A. Gilman, T. W. Rall, and F. Murad, editors. Macmillan, New York. 957–979.Google Scholar
  2. 2.
    Kay, L. W. 1972. Sterilization, disinfection, and the antiseptics.In Drugs in Dentistry. John Wright & Sons. 183–203.Google Scholar
  3. 3.
    Suzuki, Y., S. Nakamura, K. Sugiyama, andH. Furuta. 1987. Differences of Superoxide production in blood leukocytes stimulated with thymol between human and non-human primates.Life Sci. 41:1659–1664.Google Scholar
  4. 4.
    Suzuki, Y., K. Sugiyama, andH. Furuta. 1985. Eugenol-mediated Superoxide generation and cytotoxicity in guinea pig neutrophils.Jpn. J. Pharmacol. 39:381–386.Google Scholar
  5. 5.
    Suzuki, Y., T. Morita, K. Sugiyama, andH. Furuta. 1985. Stimulation of neutrophil superoxide generation system with eugenol.Jpn. J. Oral Biol. 27:338–340.Google Scholar
  6. 6.
    Klebanoff, S. J., andR. A. Clark. 1978. The Neutrophil: Function and Clinical Disorders. North-Holland Publishing, Amsterdam. 409–446.Google Scholar
  7. 7.
    Margoliash, E. andN. Frohwirt. 1959. Spectrum of horse heart cytochromec.Biochem. J. 71:570–572.Google Scholar
  8. 8.
    Beutler, E., andM. C. Baluda. 1964. Simplified determination of blood adenosine triphosphate using the firefly system.Blood 23:688–698.Google Scholar
  9. 9.
    Newburger, P. E., M. E. Chovaniec, andH. J. Cohen. 1980. Activity and activation of the granulocyte superoxide-generating system.Blood 55:85–92.Google Scholar
  10. 10.
    Sbarra, A. J., andM. L. Karnovsky. 1959. The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles of polymorphonuclear leukocytes.J. Biol. Chem. 234:1355–1362.Google Scholar
  11. 11.
    Nakagawara, M., K. Takeshige, J. Takamatsu, S. Takahashi, J. Yoshitake, andS. Minakami. 1986. Inhibition of superoxide production and Ca2+ mobilization in human neutrophils by halothane, enflurane, and isoflurane.Anesthesiology 64:4–12.Google Scholar
  12. 12.
    Goldstein, I. M., S. Lind, S. Hoffstein, andG. Weissmann. 1977. Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro: Reduction of lysosomal enzyme release and Superoxide anion production.J. Exp. Med. 146:483–494.Google Scholar
  13. 13.
    Takeshige, K., andS. Minakami. 1981. Involvement of calmodulin in phagocytic respiratory burst of leukocytes.Biochem. Biophys. Res. Commun. 99:484–490.Google Scholar
  14. 14.
    Moon, B. C., M. J. Girotti, S. F. G. Wren, R. Dawson, andD. Brar. 1986. Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphatereduced oxidase activity.Arch. Surg. 121:73–76.Google Scholar
  15. 15.
    Whitin, J. C., andH. J. Cohen. 1985. Dissociation between aggregation and Superoxide production in human granulocytes.J. Immunol. 134:1206–1211.Google Scholar
  16. 16.
    Hisayama, T., andI. Takayanagi. 1983. Increased45Ca-efflux from smooth muscle microsomes by a rise in extramicrosomal Ca ion concentration, and the effect of thymol.J. Pharm. Pharmacol. 35:532–533.Google Scholar
  17. 17.
    Cox, J. A., A. Y. Jeng, N. A. Sharkey, P. M. Blumberg, andA. I. Tauber. 1985. Activation of the human neutrophil nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase by protein kinase c.J. Clin. Invest. 76:1932–1938.Google Scholar
  18. 18.
    Papini, E., M. Grzeskowiak, P. Bellavite, andF. Possi. 1985. Protein kinase c phosphorylates a component of NADPH oxidase of neutrophils.FEBS Lett. 190:204–208.Google Scholar
  19. 19.
    Castagna, M., Y. Tarai, K. Kaibuchi, K. Sano, U. Kikkawa, andY. Nishizuka. 1982. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol ester.J. Biol. Chem. 257:7847–7851.Google Scholar
  20. 20.
    Suzuki, Y., andR. I. Lehrer. 1980. NAD(P)H oxidase activity in human neutrophils stimulated by phorbol myristate acetate.J. Clin. Invest. 66:1409–1418.Google Scholar
  21. 21.
    Schatzman, R. C., B. C. Wise, andJ. F. Kuo. 1981. Phospholipid-sensitive calcium-dependent protein kinase: Inhibition by anti-psychotic drugs.Biochem. Biophys. Res. Commun. 98:669–676.Google Scholar
  22. 22.
    Cohen, H. J., andM. E. Chovaniec. 1978. Superoxide production by digitonin-stimulated guinea pig granulocytes: The effects ofn-ethyl maleimide, divalent cations, and glycolytic and mitochondrial inhibitors on the activation of the superoxide generating system.J. Clin. Invest. 61:1088–1096.Google Scholar
  23. 23.
    Cohen, H. J., M. E. Chovaniec, M. K. Wilson, andP. E. Newburger. 1982. Con A-stimulated superoxide production by granulocytes: Reversible activation of NADPH oxidase.Blood 60:1188–1194.Google Scholar
  24. 24.
    Curnutte, J. T., B. M. Babior, andM. L. Karnovsky. 1979. Fluoride-mediated activation of the respiratory burst in human neutrophils: A reversible process.J. Clin. Invest. 63:637–647.Google Scholar
  25. 25.
    English, D., M. Schell, A. Siakotos, andT. G. Gabig. 1986. Reversible activation of the neutrophil superoxide generating system by hexachlorocyclohexane: Correlation with effects on a subcellular superoxide-generating fraction.J. Immunol. 137:283–290.Google Scholar
  26. 26.
    Smith, R. J., B. J. Bowman, andS. S. Iden. 1984. Stimulation of the human neutrophil superoxide anion-generating system with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine.Biochem. Pharmacol. 33:973–978.Google Scholar
  27. 27.
    Melloni, E., S. Pontremoli, F. Salamino, B. Sparatore, M. Michetti, O. Sacco, andB. L. Horecker. 1986. ATP induces the release of a neutral serine proteinase and enhances the production of superoxide anion in membranes from phorbol ester-activated neutrophils.J. Biol. Chem. 261:11437–11439.Google Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • Yukio Suzuki
    • 1
  • Hiroaki Furuta
    • 1
  1. 1.Department of PharmacologyOkayama University Dental SchoolOkayamaJapan

Personalised recommendations