Skip to main content
SpringerLink
Log in
Book cover

Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2 pp 189–196Cite as

Interaction of PGH Synthase Isozymes-1 and -2 with Nonsteroidal Anti-Inflammatory Drugs

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 400))

Abstract

There are two isozymes of prostaglandin endoperoxide (PGH) synthase (cyclooxygenase) called PGH synthase (PGHS)-1 and -2 or COX I and II. Both isozymes are able to catalyze the conversion of arachidonic acid to PGH2, the committed step in the formation of prostaglandins and thromboxane. PGHS-1 is present in virtually all mammalian tissues and organs (although not necessarily in all cells within an organ). In contrast, PGHS-2 is detectable by northern blotting only in a few tissues including prostate and brain. PGHS-2 has been detected in association with differentiation and cell turnover in cultured mammalian cells. The expression of this enzyme can be induced by several different cytokines and by phorbol esters. In particular, increases in PGHS-2 expression can be observed in activated macrophages. Although PGHS-1 (PGHS-1) has long been thought to be the site of action of non-steroidal anti-inflammatory drugs (NSAIDs), the discovery of a second isozyme (PGHS-2) and its potential association with inflammation has suggested that this latter enzyme may actually be the principal therapeutic target of NSAIDs. Using cDNAs for murine PGHS-1 and PGHS-2, we have expressed these two enzymes in vitro in cos-1 cells and compared the relative sensitivities of these enzymes to a series of common NSAIDs. Our results have established that murine PGHS-1 and -2 are pharmacologically distinct.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Meade E.A., Smith, W.L. and Dewitt, D.L. J. Lipid Med. 6:119–124, 1993.

    CAS  Google Scholar 

  2. Meade E.A., Smith, W.L. and Dewitt, D.L. J. Biol. Chem. 268:6610–6614, 1993.

    PubMed  CAS  Google Scholar 

  3. Rome, L.H. and Lands, W.E.M. Proc. Natl. Acad. Sci. USA 72:4863–4865, 1975.

    Article  PubMed  CAS  Google Scholar 

  4. Kulmacz, R.J. and Lands, W.E.M. J. Biol. Chem. 260:12572–12578, 1985.

    PubMed  CAS  Google Scholar 

  5. Walenga, R.W., Wall, S.F., Setty, B.N.Y. and Stuart, M.J. Prostaglandins, 31:625–637, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Haddock, R.E., Jeffery, D.J., Lloyd, J.A. and Thawley, A.R. Xenobiotics 14:327–337, 1984.

    Article  CAS  Google Scholar 

  7. Yokoyama, C. and Tanabe, T. Biochem. Biophys. Res. Commun. 165:888–894, 1989.

    Article  PubMed  CAS  Google Scholar 

  8. Kraemer, S.A., Meade, E.A. and Dewitt, D.L. Arch. Biochem. Biophys. 293:391–400, 1992.

    Article  PubMed  CAS  Google Scholar 

  9. Fletcher, B.S., Kujubu, D.A., Perrin, D.M. and Herschman, H.R. J. Biol. Chem. 267:4338–4344, 1992.

    PubMed  CAS  Google Scholar 

  10. Simmons D.L., Xie, W., Chipman, J.G. and Evett, G.E. In: Prostaglandins, Leukotrienes, Lipoxins, and PAF. (Ed. J.M. Bailey), Plenum Press, New York, 1991, pp. 67–78.

    Google Scholar 

  11. Dewitt D.L, Day, J.S., Sonnenburg, W.K. and Smith, W.L. J. Clin. Invest. 72:1882–1888, 1983.

    Article  PubMed  CAS  Google Scholar 

  12. Funk C.D., Funk, L.B., Kennedy, M.E., Pong, A.S. and Fitzgerald, G.A. FASEB 15:2304–2312, 1991.

    Google Scholar 

  13. Kujubu D.A., Reddy, ST., Fletcher, B.S. and Herschman, H.R. J. Biol. Chem. 268:5425–5430, 1993.

    PubMed  CAS  Google Scholar 

  14. O’Banion M.K., Winn, V.D. and Young, D.A. Proc. Natl. Acad. Sci. USA 89:4888–4892, 1992.

    Article  CAS  Google Scholar 

  15. Lee S.H., Soyoola, E., Chanmugam, P., Hart, S., Sun, W., Zhong, H., Liou, S., Simmons, D. and Hwang, D. J. Biol. Chem. 267:25934–25938, 1992.

    PubMed  CAS  Google Scholar 

  16. O’Sullivan, G.M., Chilton, F.H., Huggins, E.M., Jr. and McCall, C.E. J. Biol. Chem. 267:14547–14550, 1992.

    CAS  Google Scholar 

  17. O’Sullivan, M.G., Huggins, E.M., Meade, E.A., Dewitt, D.L. and McCall, C.E. Biochem. Biophys. Res. Commun. 187:1123–1127, 1992.

    Article  CAS  Google Scholar 

  18. Maier, J.A.M., Hla, T. and Maciag, T. J. Biol. Chem. 265:10805–10808, 1990.

    PubMed  CAS  Google Scholar 

  19. Jones, D.A., Carlton, D.P., Mclntyre, T.M., Zimmerman, G.A. and Prescott, S.M. J. Biol. Chem., 268:9049–9054, 1993.

    PubMed  CAS  Google Scholar 

  20. Sano, H., Hla, T., Maier, J.A.M., Crofford, L.J., Case, J.P., Maciag, T. and Wilder, R.L. J. Clin. Invest., 89:97–108, 1992.

    Article  PubMed  CAS  Google Scholar 

  21. Sirois, J. and Richards, J.S. J. Biol. Chem. 267:6382–6388, 1992.

    PubMed  CAS  Google Scholar 

  22. Sirois, J., Simmons, D.L. and J.S. Richards. J. Biol. Chem. 267:11586–11592, 1992.

    PubMed  CAS  Google Scholar 

  23. Kujubu, D.A. and Herschman, H.R. J. Biol. Chem. 267:7991–7994, 1992.

    PubMed  CAS  Google Scholar 

  24. Masferrer, J.L., Seibert, K., Zweifel, B. and Needleman, P. Proc. Natl. Acad. Sci. USA 89:3917–3921, 1992.

    Article  PubMed  CAS  Google Scholar 

  25. Jonat, C., Rahmsdorf, H.J., Park, K., Cato, A.C., Gebel, S., Ponta, H. and Herrlich, P. Cell 62:1189–1204, 1990.

    Article  PubMed  CAS  Google Scholar 

  26. Smith, W.L. Am. J. Physiol. 263:F181–F191, 1992.

    PubMed  CAS  Google Scholar 

  27. Toh, H. FEBS Lett. 258:317–319, 1989.

    Article  PubMed  CAS  Google Scholar 

  28. Kujubu D.A., Fletcher, B.S., Varnum, B.C., Lim, R.W. and Herschman, H.R. J. Biol. Chem. 266:12866–12872, 1991.

    PubMed  CAS  Google Scholar 

  29. Dewitt D.L., El-Harith, E.A., Kraemer, S.A., Andrews, M.J., Yao, E., Armstrong, R.L. and Smith, W.L. J. Biol. Chem. 265:5192–5198, 1990.

    PubMed  CAS  Google Scholar 

  30. Shimokawa, T. and Smith, W.L. J. Biol. Chem. 266:6168–6173, 1991.

    PubMed  CAS  Google Scholar 

  31. Shimokawa, T., Kulmacz, R.J., DeWitt, D.L. and Smith, W.L. J. Biol. Chem. 265:20073–20076, 1990.

    PubMed  CAS  Google Scholar 

  32. Shimokawa, T. and Smith, W.L. J. Biol. Chem. 267:12387–12392, 1992.

    PubMed  CAS  Google Scholar 

  33. Otto, J.C., DeWitt, D.L. and Smith, W.L. J. Biol. Chem. 268:18234–18242, 1993.

    PubMed  CAS  Google Scholar 

  34. Simonson, M.S., Wolfe, J.A., Konieczkowski, M., Sedor, J.R. and Dunn, M.J. Mol. Endocrinol. 5:441–451, 1991.

    Article  PubMed  CAS  Google Scholar 

  35. DeWitt, D.L., Kraemer, S.A. and Meade, E.A. In: Prostaglandins and Related Compounds II. Vol. 21, (Ed. B. Samuelsson) Raven Press, New York, 1991, pp. 75–90.

    Google Scholar 

  36. Oshima, T., Yoshimoto, T., Yamamoto, S., Kumegawa, M., Yokoyama, C. and Tanabe, T. J. Biol. Chem. 266:13621–13626, 1991.

    PubMed  CAS  Google Scholar 

  37. Smith, W.L. and D.L. DeWitt; unpublished observations.

    Google Scholar 

  38. Herschman, H.R. Ann. Rev. Biochem. 60:281–319, 1991.

    Article  PubMed  CAS  Google Scholar 

  39. Ryseck, R., Raynoschek, C., Macdonald-Bravo, H., Dorfman, K. and Bravo, R. Cell Growth Differen., 3:443–450, 1992.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Michigan State University, East Lansing, Michigan, 48824, USA

    William L. Smith, Elizabeth A. Meade & David L. Dewitt

Authors
  1. William L. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth A. Meade
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David L. Dewitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wayne State University, Detroit, Michigan, USA

    Kenneth V. Honn

  2. Free University Berlin, Berlin, Germany

    Santosh Nigam

  3. Vanderbilt University, Nashville, Tennessee, USA

    Lawrence J. Marnett

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Smith, W.L., Meade, E.A., Dewitt, D.L. (1997). Interaction of PGH Synthase Isozymes-1 and -2 with Nonsteroidal Anti-Inflammatory Drugs. In: Honn, K.V., Nigam, S., Marnett, L.J. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2. Advances in Experimental Medicine and Biology, vol 400. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5325-0_28

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5325-0_28

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7430-5

  • Online ISBN: 978-1-4615-5325-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation