NITRIC-OXIDE RELEASE IN RESPONSE TO STIMULATION OF NONADRENERGIC, NONCHOLINERGIC NERVES

The nature of the inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. In a first series of experiments, circular muscle strips were mounted in organ baths filled with aerated Krebs-Ringer solution for isometric tension recording. During a norepinephrine-induced contraction and in the presence of atropine, nitric oxide (NO) induced tetrodotoxin-resistant relaxations that were similar to the NANC relaxations obtained by electrical stimulation and acetylcholine (ACh). Inhibition of the NO biosynthesis by N(G)-monomethyl-L-arginine (L-NMMA) and N(G)-nitro-L-arginine (L-NNA) resulted in an increase in basal tension and inhibited the relaxations to electrical stimulation and ACh, but not those to NO. These effects were partly reversed by L-arginine, but not by D-arginine. Hemoglobin also raised the basal tension and reduced the relaxations to electrical stimulation and ACh and abolished those to NO. In a second series of experiments, we demonstrated the release of a labile factor with vasodilator activity upon stimulation of NANC nerves of the canine ileocolonic junction using a superfusion bioassay cascade. The release of this factor was inhibited by tetrodotoxin and L-NNA, whereas it was increased by L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by hemoglobin. Our results suggest that NO or an NO-releasing substance represents the NANC neurotransmitter in the canine ileocolonic junction.