The renal cytochrome P450 system generates novel arachidonic acid metabolite

The generation of prostaglandins and other oxygenated metabolites of arachidonic acid (AA) is a complex process initiated by the release of ester-ified AA from cellular lipids. Once liberated from membrane lipids by diverse stimuli (peptide hormones, neurotransmitters and mechanical disruption), the free AA is rapidly metabolized. Metabolism of AA involves three pathways: (a) cyclooxygenase, leading to the formation of prostaglandins, thromboxane A2 (TxA2), and prostacyclin (PGI2); (b) lipoxygenases, leading to the formation of hydroxy- and dihydroxyeicosatetraenoic acids (HETEs and diHETEs) and leukotrienes; (c) cytochrome P450-dependent monoxy-genase system which metabolizes AA by an NADPH-dependent mechanism to a variety of oxygenated products such as HETEs, epoxyeicosatrienoic acids or epoxides (EETs) and their hydrolysis products, the dihydroxyeicosatrienoic acids or diols (DHTs) as well as ω and ω-1 hydroxylated acids (1–4). The pattern of AA metabolism in the kidney is distinct and AA metabolites participate in integrated renal function. Among the structures that metabolize AA via cyclooxygenase are collecting tubules (5), glomeruli (6), medullary interstitium (7) and blood vessels (8). Other structures such as the convoluted tubules have low or negligible cyclooxygenase activity (8). Lipoxygenase activity is mainly associated with leukocytes or platelets (9,10) and was reported to be present in isolated glomeruli (11).