
Diagram of Nitric Oxide (NO) and carbon monoxide (CO) disposition at synapses. These two substances have been characterized in our laboratory as atypical neurotransmitters. As gases, they cannot be stored in synaptic vesicles, released by exocytosis or bind to receptor proteins on the external surface of neurons. They are formed "on demand" by activation of their biosynthetic enzymes. Neuronal depolarization leads to calcium influx that binds to calmodulin, stimulating NO synthase as well as heme oxygenase-9. Both NO and CO diffuse into adjacent cells to activate guanylyl cyclase to form cyclic GMP. Additionally, NO S-nitrosylates a wide range of proteins.