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Research ArticleArticle

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Daniel L. Simmons, Regina M. Botting and Timothy Hla
Pharmacological Reviews September 2004, 56 (3) 387-437; DOI: https://doi.org/10.1124/pr.56.3.3
Daniel L. Simmons
The Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah (D.L.S.); The William Harvey Research Institute, St. Bartholomew's and William and Mary Medical College, London, England (R.M.B.); and Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, Farmington, Connecticut (T.H.)
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Regina M. Botting
The Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah (D.L.S.); The William Harvey Research Institute, St. Bartholomew's and William and Mary Medical College, London, England (R.M.B.); and Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, Farmington, Connecticut (T.H.)
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Timothy Hla
The Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah (D.L.S.); The William Harvey Research Institute, St. Bartholomew's and William and Mary Medical College, London, England (R.M.B.); and Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, Farmington, Connecticut (T.H.)
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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most highly utilized classes of pharmaceutical agents in medicine. All NSAIDs act through inhibiting prostaglandin synthesis, a catalytic activity possessed by two distinct cyclooxygenase (COX) isozymes encoded by separate genes. The discovery of COX-2 launched a new era in NSAID pharmacology, resulting in the synthesis, marketing, and widespread use of COX-2 selective drugs. These pharmaceutical agents have quickly become established as important therapeutic medications with potentially fewer side effects than traditional NSAIDs. Additionally, characterization of the two COX isozymes is allowing the discrimination of the roles each play in physiological processes such as homeostatic maintenance of the gastrointestinal tract, renal function, blood clotting, embryonic implantation, parturition, pain, and fever. Of particular importance has been the investigation of COX-1 and -2 isozymic functions in cancer, dysregulation of inflammation, and Alzheimer's disease. More recently, additional heterogeneity in COX-related proteins has been described, with the finding of variants of COX-1 and COX-2 enzymes. These variants may function in tissue-specific physiological and pathophysiological processes and may represent important new targets for drug therapy.

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Pharmacological Reviews: 56 (3)
Pharmacological Reviews
Vol. 56, Issue 3
1 Sep 2004
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Research ArticleArticle

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Daniel L. Simmons, Regina M. Botting and Timothy Hla
Pharmacological Reviews September 1, 2004, 56 (3) 387-437; DOI: https://doi.org/10.1124/pr.56.3.3

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Research ArticleArticle

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Daniel L. Simmons, Regina M. Botting and Timothy Hla
Pharmacological Reviews September 1, 2004, 56 (3) 387-437; DOI: https://doi.org/10.1124/pr.56.3.3
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  • Article
    • Abstract
    • I. Cyclooxygenase Isozymes
    • II. Pharmacological Actions of Cyclooxygenase Isozyme-Generated Prostanoids
    • III. Regulation of Expression of Cyclooxygenase-1 and -2
    • IV. Cyclooxygenase Isozymes in Human Disease
    • V. Cyclooxygenase Isozymes and the Future
    • Acknowledgments
    • Footnotes
    • References
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