title: Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties.
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.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. bkis@wfubmc.edu
authors.forename: Bela
authors.initials: B
authors.lastname: Kis
authors.forename: James A
authors.initials: JA
authors.lastname: Snipes
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D000082:Acetaminophen; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3