Abstract
Cyclooxygenase (COX)-3, a novel COX splice variant, was suggested as the key to unlocking the mystery of the mechanism of action of acetaminophen. Although COX-3 might have COX activity in canines, and this activity might be inhibited by acetaminophen, its low expression level and the kinetics indicate unlikely clinical relevance. In rodents and humans, COX-3 encodes proteins with completely different amino acid sequences than COX-1 or COX-2 and without COX activity; therefore, it is improbable that COX-3 in these species plays a role in prostaglandin-mediated fever and pain. The aim of this review is to evaluate the literature that seeks to point out critical theoretical and methodological limitations of the COX-3 studies that led several investigators to scientifically questionable conclusions.
Footnotes
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This work was supported by Grants HL30260, HL66074, HL65380, and DK62372 from the National Institutes of Health and American Heart Association-Bugher Foundation Award 0270114N (to D.W.B.).
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doi:10.1124/jpet.105.085431.
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ABBREVIATIONS: NSAID, nonsteroidal anti-inflammatory drug; COX, cyclooxygenase; PCOX, partial cyclooxygenase(s); PCR, polymerase chain reaction; bp, base pair(s); RT, reverse transcription; LPS, lipopolysaccharide; NS398, N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide; COVAP, cyclooxygenase variant protein.
- Received February 24, 2005.
- Accepted May 5, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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