Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of a number of inflammatory diseases and are believed to act via inhibition of the enzyme cyclooxygenase (COX). This enzyme catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDs are efficacious anti-inflammatory agents, significant side effects limit their use. Recently two forms of COX were identified — a constitutively expressed COX-1 and a cytokine-inducible COX-2. Potent anti-inflammatory agents like the glucocorticoids are known to inhibit specifically the expression of COX-2 while commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2. These findings have led to the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1), whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2. We have examined the relative distribution of COX-1 and COX-2 in both normal and inflamed tissues and report that COX-1 expression dominates normal tissues while COX-2 mRNA is induced at the inflammatory site. Furthermore, compounds that selectively inhibit COX-2 are anti-inflammatory without gastric toxicity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
DeWitt, D. Biochim. Biophys. Acta. 1083:121–134, 1991.
Raz, A., Wyche, A., Siegel, N. and Needleman, P. J. Biol. Chem. 263:3022–3028, 1988.
Fu, J., Masferrer, J.L., Seibert, K., Raz, A. and Needleman, P. J. Biol. Chem. 265:16737–16740, 1990.
Raz, A., Wyche, A., and Needleman, P. Proc. Natl. Acad. Sci., USA 86:1657–1661, 1989.
Masferrer, J.L., Seibert, K., Zweifel, B.S. and Needleman, P. Proc. Natl. Acad. Sci., USA 89:3917–3921, 1992.
Masferrer, J.L., Zweifel, B.S., Seibert, K. and Needleman, P. J. Clin. Invest. 86:1375–1379, 1990.
Xie, W., Chipman, J.G., Robertson, D.L., Erikson, R.L. and Simmons, D.L. Proc. Natl. Acad. Sci. USA 88:2692–2696, 1991.
Kujubu, D.A., Fletcher, B.S., Varnum, B.C., Lim, R.W. and Herschman, H.R. J. Biol. Chem. 266:12866–12872, 1991.
O’Banion, M.K., Sadowski, H.B., Winn, V. and Young, D.A. J. Biol. Chem. 266:23261–23267, 1991.
Fletcher, B.S., Kujubu, D.A., Perrin, D.M. and Herschman, H.R. J. Biol. Chem. 267:4338:4344, 1992.
Sirois, J. and Richards, J.S. J. Biol. Chem. 267:6382–6388, 1992.
Kujubu, D.A. and Herschman, H.R. J. Biol. Chem. 267:7991–7994, 1992
O’Banion, M.K., Winn, V. and Young, D.A. Proc. Natl. Acad. Sci. USA 89:4888–4892, 1992.
Kujubu, D.A., Reddy, S.T., Fletcher, B.S. and Herschman, H. J. Biol. Chem. 268:5425–5430, 1993.
Futaki, N., Arai, I., Hamasak, S., Takahashi, S., Higuchi, S. and Otomo, S. J. Pharm. Pharmacol. 45:753–755, 1992.
Futaki, N., Yoshikawa, K., Yumiko, H., Arai, I., Higuchi, S., Izuka, H. and Otomo, S. Ge. Pharmac. 24:105–110, 1993.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Isakson, P. (1997). Distribution of Cox-1 and Cox-2 in Normal and Inflamed Tissues. 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_24
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5325-0_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7430-5
Online ISBN: 978-1-4615-5325-0
eBook Packages: Springer Book Archive