Intricate regulation of nitric oxide synthesis in neurons

There is little doubt that nitric oxide (NO) is one of the most important second messengers yet to be discovered, particularly in relation to its diverse roles in the regulation of neuronal function. As expected, synthesis of such a multifunctional molecule has to be under very tight control. For example, there is evidence that the rate of production of NO in neurons is regulated by several second messengers and their related protein kinases. NO by itself is also able to elicit negative feedback on the activity NO synthase (NOS) to attenuate its own rate of synthesis. Furthermore, NO modulates the release of neurotransmitters and alters the sensitivity of receptors that are coupled to stimulation of its synthesis. In healthy neurons, all of these intricate mechanisms are expected to cross-talk in harmony to result in the generation of optimal amounts of NO.