Figure 4.

Prostaglandin biosynthesis and transport. Illustration of the synthesis of bioactive eicosanoids including prostaglandin E2 (PGE2), epoxyeicosatrienoic acids (EETs), and hydroxyeicosatetraenoic acids (HETEs). These arachidonic acid metabolites are generated principally by cyclooxygenase (COX), lipooxygenase (LOX), and CYP450 enzymes (CYP2C, CYP4A, and CYP4F isoforms). HETEs and EETs have vasoconstrictive and vasodilatory effects, respectively, in blood vessels and the kidney, and phase II metabolism via glucuronidation (including UGT2B7 and UGT1A9) plays a role in bioinactivation, limiting the availability of these compounds for cellular processes. Transporters, including "drug" transporters like OAT3, regulate intratissue and intracellular uptake and efflux of various eicosanoids in the brain and elsewhere. [Colour figure can be viewed at wileyonlinelibrary.com]