nNOS (Neuronal Nitric Oxide Synthase)

Human nitric oxide synthases are a family of enzymes responsible for the synthesis of nitric oxide from L-arginine and molecular oxygen. There are at least three nitric oxide synthases; NOS I, also known as neuronal NOS or nNOS, NOS II, which is referred to as inducible NOS or iNOS and NOS III, also known as endothelial NOS or eNOS. As suggested by their nomenclature, these enzymes have different cellular distribution and are subjected to different regulatory mechanisms. NOS III, like NOS I, is a constitutive form of NOS and produces picomolar quantities of nitric oxide (NO) which plays a role in signal transmission and results in physiological effects. In the gastrointestinal tract, NO plays a protective role where it has direct microbiocidal properties and acts as a first line of mucosal defence against luminal organisms in the stomach.

nNOS plays a role in  the upregulation of microglial phospho-p38 MAPK. Such p38 MAPK activation in microglia is consistent with a potential role in the development of morphine antinociceptive tolerance.