ABSTRACT

The gas nitric oxide (NO) is a novel messenger in the nervous system that has revolutionized our way of thinking about neuronal transmission. According to our current view, two main types of signaling molecules are used by neurons to communicate with each other: these are the “ classical” neurotransmitters, such as, for example, acetylcholine, glutamate, and y-aminobutyric acid (GABA), and a number of biologically active small peptides. Both are packaged and released from synaptic vesicles, albeit of different types; their spatial signaling is, in gen­ eral terms, restricted to synaptic sites* where they bind to transmembrane recep­ tors. The action of neurotransmitters is usually concluded with the crucial contri­ bution of uptake pumps or by inactivation carried out by specific enzymes. NO is an unconventional transmitter as it is not packaged in vesicles and it can cross cell membranes rapidly, diffusing from the site of production in the absence of any specialized release machinery (2). Therefore, NO signaling is not restricted to defined synapses; rather it diffuses through cell membranes, being able to bind and influence numerous protein targets. Since NO cannot be stored and released by the cell, it is generated when needed by a complex family of nitric oxide

synthase (NOS) enzymes. Moreover, it cannot be inactivated by conventional mechanisms and is therefore regulated at the level of biosynthesis.