Nitric oxide in the brain: Looking at two sides of the same coin

BACKGROUND- The importance of nitric oxide (NO .) is apparent from its ubiquitous nature and the diversity of physiologic functions ascribed to this free radical. Nitric oxide is generated by constitutive and inducible isozymes of the dioxygenase nitric oxide synthase. This enzyme catalyzes the oxidation of L-arginine to L-citrulline and NO . via a multistep process in which molecular oxygen is incorporated into the metabolites and nicotinamide adenine dinucleotide phosphate (reduced form) is the source of electrons for this oxidation. A discussion of the enzymology is presented, and areas of continued debate are pointed out. REVIEW SUMMARY- In the brain, which contains both isoforms of nitric oxide synthase, the enzyme is localized in the endothelial cells of the vasculature, in the astrocytic glial cells, and in specific neurons, where expression is a dynamic and highly regulated process. Although guanylate cyclase is the best characterized target of NO ., other potentially important sites of reaction have been described, including interactions with iron-sulfur aconitases and activation of glyceraldehyde-3-phosphate dehydrogenase. CONCLUSION- Among the physiologic and pathophysiologic roles postulated for NO . are regulation of cerebral blood flow under normal and ischemic conditions, mediation of neurotoxicity associated with ischemia/reperfusion injury, and intercellular communication in neural development and synaptic plasticity. In clinical situations where the production of superoxide is enhanced, reaction with NO . can generate peroxynitrite, which may itself or through decomposition contribute to cytotoxicity.