Presence of NADPH-cytochrome P450 reductase in central catecholaminergic neurones

The cytochrome P450-containing mixed function oxidases metabolize a variety of endogenous and exogenous compounds including drugs, carcinogens, fatty acids and steroids. Mixed function oxidases have been detected in several tissues, including brain. The enzyme system consists of a lipid fraction (phosphatidylcholine), cytochrome P450 and NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase has been purified to apparent homogeneity and demonstrated to supply reducing equivalents from NADPH to cytochrome P450 (refs 5-7). Detection of NADPH-cytochrome P450 reductase thus represents an indirect means of demonstrating the presence of cytochrome P450. Although the role of cytochrome P450 in the central nervous system (CNS) is not known, it may include such different functions as metabolism of xenobiotics, aromatization of androgens to oestrogens and the formation of catecholoestrogens. Despite the potentially very important role(s) of cytochrome P450 in brain function, its exact regional distribution remains essentially unknown. Using a specific antibody against rat liver NADPH-cytochrome P450 reductase in combination with immunohistochemical techniques, we have now localized this enzyme to define catecholamine (CA)-containing structures of the rat and monkey brain.