ADP-ribosylation as a mechanism for the action of nitric oxide in the nervous system.

Nitric oxide (NO.) is a unique biological messenger molecule in the central and peripheral nervous systems. The molecular targets of NO. are expanding, as are its physiologic and pathophysiologic roles in the nervous system. NO. may play a role in synaptic plasticity and nervous system morphogenesis and regulate neurotransmitter release and gene expression. It functions as a nonadrenergic, noncholinergic neurotransmitter in the gastrointestinal tract, where it mediates peristalsis through smooth muscle relaxation, and in the penis, where it regulates erectile function. NO. is emerging as an important endogenously derived neurotoxin that may contribute to neuronal cell death in a variety of disorders of the nervous system. NO. may mediate its neurotoxic properties through DNA damage and the subsequent activation of poly (ADP-ribose) synthetase which depletes neurons of their energy stores.