NO (Nitric Oxide) is formed endogenously by a family of enzymes known as NOS (NO Synthases). The distribution of different isoforms of NOS is largely related to their respective functions. Three distinct isoforms of NOS have been identified: nNOS (also kn ...own as NOSI and NOS-1) being the isoform first found (and predominating) in neuronal tissue, iNOS (also known as NOSII and NOS-2) which is inducible in a wide range of cells and tissues and eNOS (also known as NOSIII and NOS-3) isoform first found in vascular endothelial cells. Glutamate, the major excitatory neurotransmitter in the brain, is the most effective activator of NO biosynthesis in most brain regions. Recent studies show that NO actions in brain and muscle also rely crucially upon the association of nNOS with specific protein complexes in neurons and muscle cells, respectively. These physical interactions with nNOS allow for integration of NO signaling into distinct transduction cascades in specific cell types. In the brain, the 160kDa nNOS-Alpha is the predominant splice variant, and contains an N-terminal PSD/Discs-large/ZO-1 homologous (PDZ)-binding domain, which anchors this complex to the postsynaptic density in the vicinity of the NMDAR. The PDZ domain of nNOS binds to a similar PDZ domain from the postsynaptic density protein, PSD95, which in turn binds to the cytosolic tail of the NMDAR.
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