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Cyclooxygenase-2: Biology of Prostanoid Biosynthesis and Metabolism

  1. Paola Patrignani1,
  2. Ratree Maenthaisong2,3,
  3. Stefania Tacconelli1

Published Online: 15 JUN 2012

DOI: 10.1002/9780470015902.a0023205



How to Cite

Patrignani, P., Maenthaisong, R. and Tacconelli, S. 2012. Cyclooxygenase-2: Biology of Prostanoid Biosynthesis and Metabolism. eLS. .

Author Information

  1. 1

    G. d'Annunzio University, Department of Neuroscience and Imaging, School of Medicine, and Center of Excellence on Aging (CeSI), Chieti, Italy

  2. 2

    Mahidol University, Department of Pharmacology, Bangkok, Thailand

  3. 3

    Mahasarakham University, Department of Clinical Pharmacy and Research, Mahasarakham, Thailand

Publication History

  1. Published Online: 15 JUN 2012


Cyclooxygenase (COX)-2 is a key enzyme in the conversion of arachidonic acid (AA) to prostanoids. Inhibition of COX-2-dependent prostanoids by nonsteroidal anti-inflammatory drugs (NSAIDs) (both traditional(t) and selective for COX-2, named coxibs) is involved in their efficacy in affecting pain and inflammation and in reducing the recurrence of colorectal polyps. However, the use of tNSAIDs and coxibs is associated with a small but consistent increase of cardiovascular (CV) risk which is believed to be due to the reduction of the biosynthesis of endothelial COX-2-dependent prostacyclin (PGI2). Novel knowledge on the biology of COX-2 show that endocannabinoids may be the substrate for the COX-isozyme. Endocannabinoids and endocannabinoid-derived products of COX-2-mediated oxidative metabolism serve a variety of regulatory functions. Interference with endocannabinoid metabolism by NSAIDs might contribute to their pharmacological effects.

Key Concepts:

  • COX-2 is overexpressed in inflammation and cancer mainly through posttranscriptional mechanisms involving stabilisation of its mRNA.

  • Enhanced cytoplasmic levels of RNA stability factors, such as HuR, and reduced levels of microRNAs govern COX-2 mRNA stability and translational efficiency.

  • The constitutive expression of COX-2 in endothelial cells plays an important role in cardiovascular homoeostasis through the generation of prostacyclin.

  • COX-2 is the target of NSAIDs, traditional and coxibs, thus leading to therapeutic effects and cardiovascular hazard, in some individuals.

  • The major mechanism of action of NSAIDs is through the inhibition of the conversion of AA to biologically active prostanoids.

  • Novel knowledge on the biology of COX-2 shows that the activity of the COX-isozyme may be involved in the generation of novel biologically active lipid mediators through the metabolism of endocannabionids.

  • COX-2 might affect endocannabinoid tone by contributing to its reduction.

  • Endocannabinoids activate cannabinoid receptors to serve a variety of regulatory functions.

  • These novel actions of COX-2 may suggest their contribution to the therapeutic effects of NSAIDs.

  • The (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are inactive to inhibit the metabolism of AA by COX-2, are potent substrate-selective inhibitors of endocannabinoid oxygenation.

  • The discovery of these novel effects of (R) enantiomers of NSAIDs opens the way to develop novel analgesic drugs based on this mechanism of action.


  • COX-2;
  • prostanoids;
  • endocannabinoids;
  • NSAIDs;
  • NSAID R-enantiomers;
  • coxibs