Evidence for nitric oxide as mediator of non‐adrenergic, non‐cholinergic relaxations induced by ATP and GABA in the canine gut

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Abstract
1 The effects of haemoglobin, and the nitric oxide (NO) biosynthesis-inhibitors NG-monomethyl-l-arginine (l-NMMA), its enantiomer d-NMMA, and NG-nitro-l-arginine (l-NNA) were investigated on non-adrenergic non-cholinergic (NANC)-mediated relaxation of circular muscle strips of the canine terminal ileum and ileocolonic junction induced by electrical stimulation, adenosine 5′-triphosphate (ATP), γ-aminobutyric acid (GABA) and NO. 2 Tetrodotoxin, l-NMMA and l-NNA, but not d-NMMA, inhibited the relaxations induced by electrical stimulation, ATP and GABA, but not those in response to NO. 3 The inhibitory effect of l-NMMA and l-NNA was prevented by l-arginine, but not by d-arginine. l-Arginine did not potentiate any of the NANC relaxations. 4 Haemoglobin reduced the relaxation induced by electrical stimulation, ATP and GABA, and abolished those in response to NO. 5 Our results demonstrate that the ATP- and GABA-induced relaxations resulting from stimulaton of intramural NANC neurones, in addition to those induced by electrical impulses, are mediated by NO or a NO releasing substance and thus provide further evidence in support of the proposal that NO is the final inhibitory NANC neurotransmitter in the canine terminal ileum and ileocolonic junction.