Paracetamol-inhibitable COX-2.
Although paracetamol potently reduces pain and fever, its mechanism of action has so far not been satisfactorily explained. It inhibits both COX-1 and COX-2 weakly in vitro, but reduces prostaglandin synthesis markedly in vivo. In mouse macrophage J774.2 cells, COX-2 induced for 48 hr with high concentrations of NSAIDs is more sensitive to inhibition with paracetamol than endotoxin-induced COX-2. In the rat pleurisy model of inflammation, a second peak of COX-2 protein appears 48 hr after administration of the inflammatory stimulus, during the resolution phase of the inflammatory process. Inhibition of the activity of this late-appearing COX-2 with indomethacin or a selective COX-2 inhibitor, delays resolution and the inflammation is prolonged. Cultured lung fibroblasts also express COX-2 activity after stimulation with IL-1beta which is highly sensitive to inhibition with paracetamol. Thus, evidence is accumulating for the existence of a COX-2 variant or a new COX enzyme which can be inhibited with paracetamol.
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The William Harvey Research Institute, St Bartholomew's and the Royal London Medical and Dental School, UK.
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D004008:Diclofenac; D000082:Acetaminophen; D011451:Prostaglandin-Endoperoxide Synthases