Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Sep;92(1):63–68. doi: 10.1111/j.1476-5381.1987.tb11296.x

Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl-2,acetyl glycerol and A23187 in human neutrophils.

M M Dale 1, A Penfield 1
PMCID: PMC1853637  PMID: 2822195

Abstract

1 Indomethacin (10(-4)M) causes marked augmentation of O-2 release from human neutrophils when these are stimulated by either 1,oleoyl-2,acetylglycerol or the divalent cation ionophore, A23187, the concentration-response curve for each agent being shifted to the left and the maximum response to each increased. 2 The diacylglycerol kinase inhibitor, R59022 (10(-5)M) has effects very similar to those of indomethacin on both the 1,oleoyl-2,acetylglycerol-induced and the A23187-induced concentration-response curves for O-2 generation. 3 The diacylglycerol lipase inhibitor, RHC80267 (10(-5 M) on the other hand, has a similar effect to indomethacin on 1,oleoyl-2,acetylglycerol-induced O2- generation but, unlike indomethacin, has no effect on A23187-induced O2- generation. Comparison of the effects of these three agents provides a clue to the locus of the action of indomethacin in increasing superoxide release, suggesting that it may act as a diacylglycerol kinase inhibitor. A component of diacylglycerol lipase inhibition may also be present. It is suggested that these results could have relevance for the use of indomethacin as an anti-inflammatory agent in chronic rheumatoid diseases.

Full text

PDF
63

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Badwey J. A., Karnovsky M. L. Active oxygen species and the functions of phagocytic leukocytes. Annu Rev Biochem. 1980;49:695–726. doi: 10.1146/annurev.bi.49.070180.003403. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  3. Bromberg Y., Pick E. Unsaturated fatty acids as second messengers of superoxide generation by macrophages. Cell Immunol. 1983 Jul 15;79(2):240–252. doi: 10.1016/0008-8749(83)90067-9. [DOI] [PubMed] [Google Scholar]
  4. Cockcroft S., Bennett J. P., Gomperts B. D. Stimulus-secretion coupling in rabbit neutrophils is not mediated by phosphatidylinositol breakdown. Nature. 1980 Nov 20;288(5788):275–277. doi: 10.1038/288275a0. [DOI] [PubMed] [Google Scholar]
  5. Dale M. M., Penfield A. Superoxide generation by either 1-oleoyl-2-acetylglycerol or A23187 in human neutrophils is enhanced by indomethacin. FEBS Lett. 1985 Jun 3;185(1):213–217. doi: 10.1016/0014-5793(85)80772-9. [DOI] [PubMed] [Google Scholar]
  6. Dale M. M., Penfield A. Synergism between phorbol ester and A23187 in superoxide production by neutrophils. FEBS Lett. 1984 Sep 17;175(1):170–172. doi: 10.1016/0014-5793(84)80592-x. [DOI] [PubMed] [Google Scholar]
  7. Di Virgilio F., Lew D. P., Pozzan T. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels. Nature. 1984 Aug 23;310(5979):691–693. doi: 10.1038/310691a0. [DOI] [PubMed] [Google Scholar]
  8. Fantone J. C., Marasco W. A., Elgas L. J., Ward P. A. Stimulus specificity of prostaglandin inhibition of rabbit polymorphonuclear leukocyte lysosomal enzyme release and superoxide anion production. Am J Pathol. 1984 Apr;115(1):9–16. [PMC free article] [PubMed] [Google Scholar]
  9. Gay J. C., English D., Lukens J. N. Stimulation of neutrophil oxidative metabolism by indomethacin. Agents Actions. 1985 Jul;16(5):336–341. doi: 10.1007/BF01982869. [DOI] [PubMed] [Google Scholar]
  10. Gay J. C., Lukens J. N., English D. K. Differential inhibition of neutrophil superoxide generation by nonsteroidal antiinflammatory drugs. Inflammation. 1984 Jun;8(2):209–222. doi: 10.1007/BF00916096. [DOI] [PubMed] [Google Scholar]
  11. Gerard C., McPhail L. C., Marfat A., Stimler-Gerard N. P., Bass D. A., McCall C. E. Role of protein kinases in stimulation of human polymorphonuclear leukocyte oxidative metabolism by various agonists. Differential effects of a novel protein kinase inhibitor. J Clin Invest. 1986 Jan;77(1):61–65. doi: 10.1172/JCI112302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hannun Y. A., Loomis C. R., Merrill A. H., Jr, Bell R. M. Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J Biol Chem. 1986 Sep 25;261(27):12604–12609. [PubMed] [Google Scholar]
  13. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  14. Johnston R. B., Jr, Lehmeyer J. E. Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J Clin Invest. 1976 Apr;57(4):836–841. doi: 10.1172/JCI108359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lunec J., Blake D. R., McCleary S. J., Brailsford S., Bacon P. A. Self-perpetuating mechanisms of immunoglobulin G aggregation in rheumatoid inflammation. J Clin Invest. 1985 Dec;76(6):2084–2090. doi: 10.1172/JCI112212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muid R. E., Penfield A., Dale M. M. The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptors. Biochem Biophys Res Commun. 1987 Mar 13;143(2):630–637. doi: 10.1016/0006-291x(87)91400-8. [DOI] [PubMed] [Google Scholar]
  17. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  18. Penfield A., Dale M. M. Synergism between A23187 and 1-oleoyl-2-acetyl-glycerol in superoxide production by human neutrophils. Biochem Biophys Res Commun. 1984 Nov 30;125(1):332–336. doi: 10.1016/s0006-291x(84)80372-1. [DOI] [PubMed] [Google Scholar]
  19. Rittenhouse-Simmons S. Indomethacin-induced accumulation of diglyceride in activated human platelets. The role of diglyceride lipase. J Biol Chem. 1980 Mar 25;255(6):2259–2262. [PubMed] [Google Scholar]
  20. Robinson J. M., Badwey J. A., Karnovsky M. L., Karnovsky M. J. Superoxide release by neutrophils: synergistic effects of a phorbol ester and a calcium ionophore. Biochem Biophys Res Commun. 1984 Jul 31;122(2):734–739. doi: 10.1016/s0006-291x(84)80095-9. [DOI] [PubMed] [Google Scholar]
  21. Sutherland C. A., Amin D. Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem. 1982 Dec 10;257(23):14006–14010. [PubMed] [Google Scholar]
  22. Wilson E., Olcott M. C., Bell R. M., Merrill A. H., Jr, Lambeth J. D. Inhibition of the oxidative burst in human neutrophils by sphingoid long-chain bases. Role of protein kinase C in activation of the burst. J Biol Chem. 1986 Sep 25;261(27):12616–12623. [PubMed] [Google Scholar]
  23. Wright C. D., Hoffman M. D. The protein kinase C inhibitors H-7 and H-9 fail to inhibit human neutrophil activation. Biochem Biophys Res Commun. 1986 Mar 28;135(3):749–755. doi: 10.1016/0006-291x(86)90992-7. [DOI] [PubMed] [Google Scholar]
  24. de Chaffoy de Courcelles D. C., Roevens P., Van Belle H. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem. 1985 Dec 15;260(29):15762–15770. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES