Nitric Oxide Signaling
The chemical messenger, nitric oxide is produced by the oxidation of L-arginine by a family of enzymes known as the nitric oxide synthases (NOS).
There are three distinct forms of NOS:
- nNOS (neuronal/Type I/NOS-1/bNOS)
- iNOS (inducible/Type II/NOS-2)
- eNOS (endothelial/Type III/NOS-3)
Nitric oxide is an autocrine and paracrine signaling molecule that can diffuse through biological membranes. It has a very short duration of action (a few seconds) and its main physiological function is to contribute to the homeostasis of the vasculature. Nitric oxide inhibits smooth muscle contraction and growth, inhibits platelet aggregation and prevents leukocyte-endothelial adhesion. Nitric oxide is also involved in immune defense; it is generated by phagocytes and destroys bacteria via its action as a free radical. Targets of nitric oxide include guanylyl cyclase, which increase cGMP levels and NF-κB, which acts as a transcription factor in iNOS gene expression.
Perturbations in nitric oxide levels and signaling has been shown to occur in some disease states. People with diabetes tend to have lower global levels of nitric oxide and atherosclerotic blood vessels have impaired nitric oxide signaling pathways.
Nitric Oxide Biosynthesis Pathway
Moncada et al (1997) XIV. International Union of Pharmacology Nomenclature in Nitric Oxide Research. Pharmacol.Rev. 49 137.