Cytochrome P-450-related arachidonic acid metabolites

Arachidonic acid (AA) can be metabolized to diverse products that differ widely in their biologic activities. Depending on the cell type, AA can be metabolized by 3 pathways: cyclooxygenase, lipoxygenases, and cytochrome P-450 monooxygenases. Disease states, injury, and stress, will influence the enzymes that regulate the breakdown of AA and may favor the generation of products not usually associated with a tissue. Studies on renal eicosanoid mechanisms (all AA metabolites) can serve as a paradigm for other tissues and organs. Discrete stimulation of renal AA metabolism can occur-localized to specific cells within segments of the nephron; for example, cells of the medullary segment of the thick ascending limb of the loop of Henle (mTALH) have high cytochrome P-450 monooxygenase activity, through which novel AA metabolites are formed. These metabolites have characteristic biologic activities, inhibition of Na+-K+-ATPase activity and relaxation of blood vessels, and can be stimulated by peptide hormones. Cytochrome P-450-dependent monooxygenases are also present in the lung where, in their suggested capacity as oxygen sensors, they generate metabolites of AA that modify pulmonary vasomotion.