Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid.

Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ
Biochemistry. 2009 48 (31): 7353-5

PMID: 19603831 · PMCID: PMC2720641 · DOI:10.1021/bi900999z

Ibuprofen and mefenamic acid are weak, competitive inhibitors of cyclooxygenase-2 (COX-2) oxygenation of arachidonic acid (AA) but potent, noncompetitive inhibitors of 2-arachidonoylglycerol (2-AG) oxygenation. The slow, tight-binding inhibitor, indomethacin, is a potent inhibitor of 2-AG and AA oxygenation whereas the rapidly reversible inhibitor, 2'-des-methylindomethacin, is a potent inhibitor of 2-AG oxygenation but a poor inhibitor of AA oxygenation. These observations are consistent with a model in which inhibitors bind in one subunit of COX-2 and inhibit 2-AG binding in the other subunit of the homodimeric protein. In contrast, ibuprofen and mefenamate must bind in both subunits to inhibit AA binding.

MeSH Terms (14)

Animals Anti-Inflammatory Agents, Non-Steroidal Arachidonic Acid Arachidonic Acids Binding, Competitive Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Endocannabinoids Glycerides Ibuprofen Mefenamic Acid Mice Oxygen Protein Binding

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