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-1bΔG). Human cyclooxygenase-1bΔG was active but was not inhibited by acetaminophen. In conclusion, full length human cyclooxygenase-1b is clearly not the target of acetaminophen.