Review ■ Nitric Oxide: Actions and Pathological Roles

Nitric oxide is a unique biological messenger molecule. It mediates, in part, the immune functions of mac rophages ; it is produced by endothelial cells to mediate blood vessel relaxation; and it also serves as a neurotransmitter in the central and peripheral nervous system. Endothelial nitric oxide synthase and neuronal nitric oxide synthase are thought to be primarily constitutive, with activation induced by calcium entry into cells in the absence of protein synthesis, whereas the macrophage nitric oxide synthase is inducible with large increases in new nitric oxide synthase protein synthesis after immune stimulation. The molecular targets of nitric oxide are expanding, as are its physiological and pathophysiological roles in the nervous system. Nitric oxide may regulate neurotransmitter release, and it may play a key role in nervous system morpho genesis and synaptic plasticity and regulate gene expression. Under conditions of excessive formation, nitric oxide is emerging as an important neurotoxin in a variety of disorders of the nervous system.