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.
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
Jan M
JM
Schwab
Hermann J
HJ
Schluesener
Richard
R
Meyermann
Charles N
CN
Serhan
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