Nitric oxide: Diverse actions in the central and peripheral nervous systems

Nitric oxide (NO) has revolutionized our conceptions about neurotransmission. NO is not stored in synaptic vesicles, is not released by exocytosis, and does not mediate its action by binding to cell surface receptors. Instead, NO simply diffuses to its targets, and its actions are mediated through molecules that accept or share its unpaired electron. NO has diverse biological roles, including functions as the nitrergic transmitter of the peripheral nervous system, the major regulator of blood vessel tone, and actions as the cytotoxic agent of activated macrophages. In the CNS, NO function is just beginning to be explored, but it seems to play prominent roles in plasticity and the regulation of complex behaviors. Under conditions of excessive formation, NO has emerged as an important endogenous neurotoxin. Strategies aimed at reducing NO formation may therefore have therapeutic benefit.