Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut.
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 nonadrenergic 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), gamma-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 stimulation 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.
Boeckxstaens
G E
GE
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Antwerp-Wilrijk, Belgium.
Pelckmans
P A
PA
Bult
H
H
De Man
J G
JG
Herman
A G
AG
van Maercke
Y M
YM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004285:Dogs; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D019323:omega-N-Methylarginine
D018377:Neurotransmitter Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D001120:Arginine