Human cyclooxygenase-1b is not the elusive target of acetaminophen.
A 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.
Censarek
Petra
P
Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinik Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
Freidel
Kerstin
K
Hohlfeld
Thomas
T
Schrör
Karsten
K
Weber
Artur-Aron
AA
D000082:Acetaminophen / Q000494:pharmacology*; D017398:Alternative Splicing; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007438:Introns / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D000082:Acetaminophen; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3