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Comparative Study
Human cyclooxygenase-1b is not the elusive target of acetaminophen.
- Petra Censarek, Kerstin Freidel, Thomas Hohlfeld, Karsten Schrör, and Artur-Aron Weber.
- Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinik Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
- Eur. J. Pharmacol. 2006 Dec 3; 551 (1-3): 50-3.
AbstractA cyclooxygenase-1 splice variant (cyclooxygenase-1b), cloned from canine brain, was proposed to be an acetaminophen-sensitive enzyme. Unlike in canines, the retention of intron 1 in the human sequence results in a frame shift and predicts a truncation of the protein. We have sought to answer the question whether human cyclooxygenase-1b, if expressed, is a target of acetaminophen. Thus, we studied the pharmacology of complete human cyclooxygenase-1b in which the frame shift was corrected by site-directed mutagenesis (human cyclooxygenase-1bDeltaG). Human cyclooxygenase-1bDeltaG was active but was not inhibited by acetaminophen. In conclusion, full length human cyclooxygenase-1b is clearly not the target of acetaminophen.
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