Which one of the following inflammatory mediators is NOT derived from arachidonic acid?
The correct answer is a. Bradykinin is not derived from arachidonic acid.
Arachadonic acid (AA) is a key intermediate in inflammatory pathways. It is produced from membrane phospholipids by phospholipase A2 enzyme when tissues are damaged. In turn, arachidonic acid is converted to several potent inflammatory mediators by the action of: 1) cyclooxygenase enzymes (COX 1 and 2) found in blood vessels, smooth muscle, platelets and other organ parenchyma; and 2) intracellular 5-lipooxygenase (5-LO) expressed predominantly by immune and inflammatory cells.
Inflammatory mediators derived from arachidonic acid by the action of cyclooxygenase are together called the prostanoids. The major prostanoids are:
• Prostaglandins, particularly PGE2 which is a vasodilator and induces fever
• Prostacyclin (PGI2), which promote vasodilatation and platelet inhibition
• Thromboxane TXA2 and TXB2. TXA2 promotes vasoconstriction, platelet aggregation and activation. The actions of prostacyclin and thromboxane are in homeostatic balance.
5-lipooxygenase converts arachidonic acid into the leukotrienes.
• In particular, leukotriene D4 (LTD4) is a potent bronchoconstrictor and plays a role in the pathogenesis of acute asthma and other allergic conditions of the airways.
Both cycloogenase and the 5-lipoxegenase provide therapeutic targets for inti-inflammatory and anti-platelet drugs. Aspirin (salicylates) and the NSAIDS inhibit COX 1 and 2, hence their role as anti-platelet and anti-inflammatory drugs. Leukotriene antagonists, e.g. montelukast, inhibit 5-lipoxygenase and are used in the treatment of asthma.
(Note, bradykinin is synthesised from its circulating precursor kallikrein as part of the kinin-kallikrien system and is therefore not derived from arachidonic acid)