Nitric oxide and carbon monoxide: parallel roles as neural messengers

Nitric oxide is now appreciated to be a molecule with important signaling functions in the body. The purification and cloning of the first NO synthesizing enzyme, NO synthase (NOS), from brain has led to the characterization of the roles of NO in normal physiology and in pathogenic states. NO synthesis is regulated in a complex manner, involving the association of activatory and inhibitory proteins. The body appears to use at least one other, highly related gas in a signaling function, carbon monoxide (CO). The enzyme responsible for CO biosynthesis in brain, heme oxygenase-2 (HO2), is rapidly regulated by neurotransmitter stimulation. The role for CO as neurotransmitter is suggested by the altered intestinal motility in mice harboring a genomic deletion of HO2.