NITRIC-OXIDE - A NOVEL AUTONOMIC NEUROTRANSMITTER

Considerable evidence suggests that nitric oxide (NO) acts as a nonadr energic noncholinergic (NANC) transmitter at autonomic neuroeffector j unctions. NO is generated enzymatically from L-arginine by a constitut ive, cytosolic, Ca2(+)/calmodulin-activated NO synthase (NOS): NADPH- and tetrahydrobiopterin-dependent cytochrome P-450-type hemoprotein. E lectrophysiological and pharmacological data indicate that NO fulfils most of the criteria for a neurotransmitter. It is released from axon terminals when invaded by action potentials and mimics the effect of n erve stimulation. The changes in the mechanical and/or electrical acti vity of smooth muscle preparations in response to transmural stimulati on of NANC nerves are antagonized by inhibitors of NO synthesis or oxy hemoglobin, an NO scavenger. NO acts principally by stimulating solubl e guanylate cyclase. Studies on the histochemical localization of NOS point to the involvement of the neural L-arginine-NO pathway in the re gulation of vascular tone and of several aspects of respiratory, gastr ointestinal, and genitourinary tract functions.