Role of the L-Arginine-NO-Cyclic GMP Pathway in NANC Neurotransmission

Summary

Some noradrenergic noncholinergic (NANC) autonomic and enteric nerves utilize NO or an NO-like factor as a transmitter and have been termed nitrergic. They contain a characteristic neuronal isozyme of NO synthase (NOS). Synthesis of NO from L-arginine requires a number of cofactors, of which haem and terahydrobiopterin are the most recently recognized. The entry of Ca²⁺ produced by stimulation of nitrergic nerves activates NOS and results in release of the transmitter. It acts on the soluble guanylate cyclase of effector smooth muscle cells, resulting in a rise in the cyclic GMP level and hence relaxation. Nitrergic neuroeffector junctions in the gastrointestinal tract may also include interstitial cells. Cotransmitters, such as ATP and VIP, may be released with nitrergic transmitter. Further work is required to determine its functional interactions with other transmitters, on the modulation of NO synthesis and release, and the identification of exact nature of the nitrergic transmitter.

Based on a Symposium at the Twelfth International Congress of Pharmacology, Montreal, 29 July, 1994. The speakers, in order of their presentations, were B. Mayer (Graz, Austria), K. Sanders (Reno, Nevada, USA), N. Toda (Ohtsu, Japan), M.J. Rand (Melbourne, Australia), and G. Burnstock (London, UK).