NITRIC OXIDE

Nitric oxide (NO) is a peripheral mediator. Its significance as an important chemical mediator in CNS became apparent only about 10 years ago.

NO in nervous system is produced mainly by constitutive neuronal form of nitric oxide synthase (nNOS). It is present in roughly 2% of neurons, both short interneurons and long-tract neurons, in virtually all brain areas, with particular concentration in cerebellum and hippocampus. It occurs in cell bodies and dendrites, as well as in axon terminals, suggesting that the release of NO is not restrict to conventional neurotransmitter release sites. nNOS is calmodulin-dependent .

NO exerts its effects in two main ways:

by activation of soluble guanylate cyclase, leading to the production of cGMP, leading to various phosphorilation cascades. This “physiological” control mechanism operates at low NO concentration of about 0,1 μM/l.

by reacting with superoxide free radical, to generate peroxynitrite, a highly toxic anion, which acts by oxidizing various intracellular proteins. This requires concentration of 1- 10μM/l, which are achieved in brain ischemia.

There is good evidence that NO plays a role in long-term potentiation and depression.

NO is also believed to play an important role in the mechanisms by which ischemia causes neuronal death.