COX-3: Uncertainties and controversies

SummaryA splice variant of COX-1 named cyclooxygenase-3 (COX-3) was discovered in canine brain cells. Since then, COX-3 mRNA is found in many tissues such as canine and human cerebral cortices, human aorta, and rodent heart, endothelium, kidney and neuronal tissues.The mechanism of action of paracetamol remains unresolved. The greater sensitivity of cells containing COX-3 to paracetamol is frequently cited as indicating that the target of action of paracetamol is COX-3. Recent research indicates that paracetamol inhibits prostaglandin synthesis in cells that have a low rate of synthesis and low levels of peroxide. When the levels of arachidonic acid are low, paracetamol appears to be a selective COX-2 inhibitor. Paracetamol has predominant effects on the central nervous system because the peroxide and arachidonic acid levels in the brain are lower than at peripheral sites of inflammation. Resolving these issues requires further research using molecular biology and advanced pharmacological techniques.The aim of this article is to summarise the biochemistry of COX-3 and discuss its role with respect to the mechanism of action of paracetamol.