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Evidence for nitric oxide as mediator of non‐adrenergic, non‐cholinergic relaxations induced by ATP and GABA in the canine gut
Author(s) -
Boeckxstaens Guy E.,
Pelckmans Paul A.,
Bult Hidde,
Man Joris G.,
Herman Arnold G.,
Maercke Yvan M.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12191.x
Subject(s) - cholinergic , mediator , adrenergic , nitric oxide , nitric oxide synthase , neuroscience , parasympathomimetics , chemistry , endocrinology , cyclic gmp , medicine , biology , receptor , muscarinic acetylcholine receptor
1 The effects of haemoglobin, and the nitric oxide (NO) biosynthesis‐inhibitors N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA), its enantiomer d ‐NMMA, and N G ‐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.