Nitric oxide: a novel link between synaptic and nonsynaptic transmission

Accumulating evidence indicates that nitric oxide (NO) inhibits the function of monoamine transporters, Because the production of NO by neuronal NO synthase (nNOS) is closely related to the activation of NMDA receptors, the level of NO around nNOS-containing synapses reflects the activity of glutamate-mediated neurotransmission, Glutamate participates mainly in synaptic interactions, but with the help of NO, the strength of excitatory input might be nonsynaptically signaled to the surrounding monoaminergic neurons, which can adapt to the changes without receiving glutamatergic input and without synthesizing glutamate receptors, Thus, the effect of NO on transporters represents a new form of interneuronal communication, a nonsynaptic interaction without receptors.