Nitric oxide and peroxynitrite as factors to stimulate neurotransmitter release in the CNS

This review summarizes the stimulatory potentials of NO and peroxynitrite (OONO-) on neurotransmitter release in the central nervous system. Exogenous and endogenous NO stimulates to release neurotransmitter. NO synthesized intracellularly diffuses out through neuronal membrane and acts on the outer side of membrane to depolarize neuronal membrane, which triggers neurotransmitter release. NO-induced release of neurotransmitters is mediated by Ca2+-dependent and -independent processes. The latter process is operated by reverse process of the Na+-dependent carrier-mediated neurotransmitter uptake system or by unknown mechanisms. Ca2+-dependent release of neurotransmitter occurs in part subsequent to increase in Ca2+ influx via VDCCs, although N-type VDCCs may not involve in this action of NO because of suppression of Ca2+ influx through N-type VDCCs by NO. Participation of cGMP formation by NO on neurotransmitter release is controversial. A superoxide scavenger, Ca2+, Zn(2+)-superoxide dismutase, abolishes NO-induced neurotransmitter release and synthesized OONO- induces neurotransmitter release, indicating that OONO- participates in NO-evoked neurotransmitter release.