COX-3 the enzyme and the concept: steps towards highly specialized pathways and precision therapeutics?
Cyclooxygenases (COXs) catalyse the key rate-limiting step in prostanoid and thromboxane biosynthesis and are targets of non-steroidal anti-inflammatory drugs (NSAIDs). Until recently, the presence of only two isoforms-COX-1 and COX-2-remained in question because the potent anti-pyretic and analgesic effects of acetaminophen (paracetamol, tylenol ben-u-ron) could not be explained by either COX-1 or COX-2 blockades. A novel COX-1 splice variant termed COX-3, sensitive to acetaminophen, was recently discovered by Simmons et al., and is considered to play a key role in the biosynthesis of prostanoids known to be important mediators in pain and fever. Drugs that preferential block COX-1 also appear to act at COX-3. However the existence of COX-3 at the nucleotide sequence level in humans has been called to question. A functional COX-3 in humans is still to come underlining that the concept of COX-3 is still attractive. Here, we discuss some of the implications drawn from the identification of additional functional cyclooxygenase members in the generation of bioactive autacoids.
Schwab
Jan M
JM
Department of Neuropathology, Neuroimmunology, Medical School, Institute of Brain Research, University of Tuebingen, Calwer Str. 3, Tuebingen D-72076, Germany. jmschwab@med.uni-tuebingen.de
Schluesener
Hermann J
HJ
Meyermann
Richard
R
Serhan
Charles N
CN
D000082:Acetaminophen / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000378:metabolism; D000818:Animals; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D000082:Acetaminophen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3