NITRIC-OXIDE IN THE PERIPHERAL NERVOUS-SYSTEM

Nitric oxide (NO) is a neurotransmitter and neuromodulator in the cent ral nervous system, but this small labile substance also seems to serv e as a peripheral neurotransmitter. Abundant evidence is now available that NO, synthesized from L-arginine by NO synthase (NOS), is a nonad renergic noncholinergic relaxant transmitter of gastrointestinal smoot h muscle. Electrically induced nonadrenergic noncholinergic relaxation s are antagonized by NOS inhibitors in vitro and in vivo. In a bioassa y superfusion system, the release of a substance with the pharmacologi cal characteristics of NO from a gastrointestinal smooth muscle prepar ation was detected; also, indirect measurements (e.g. of the NO metabo lite nitrite or of the co-product of its synthesis L-citrulline) sugge st NO release. Immunohistochemistry with antibodies raised against the neuronal NOS showed immunoreactivity in cell bodies of neurones in th e myenteric plexus and in nerve fibres in the muscular layer. These da ta suggest that nerve endings, innervating smooth muscle, are able to release NO that will penetrate the cells to induce relaxation (i.e. ni trergic neurotransmission). It is unlikely that NO as such is stored a nd it is generally accepted that it is synthesized on demand when the nerve endings are excited, although the possibly of the release of a N O-containing molecule protecting it from degradation in the junction h as been proposed. Other sources than neurones (interstitial cells, smo oth muscle cells) for the NO involved in nonadrenergic noncholinergic inhibitory transmission have also been proposed. Using NADPH diaphoras e as a marker for neuronal NOS, deficiency of the nitrergic innervatio n has been shown in isolated tissue from patients with infantile hyper trophic pyloric stenosis, achalasia and Hirschsprung's disease, sugges ting that a lack of NO release might be involved in these disorders. E vidence in favour of nitrergic neurotransmission to smooth muscle has also been obtained in the respiratory and lower urinary tract, the cor pora cavernosa and some blood vessels.