Modulation of neuroeffector transmission by endogenous nitric oxide: a role for acetylcholine receptor-activated nitric oxide formation, as indicated by measurements of nitric oxide/nitrite release.
Nitric oxide (NO) synthase inhibitors enhanced nerve-mediated contractile responses in guinea pig ileum longitudinal muscle, likely via a prejunctional effect on substance P-like neuroeffector transmission. Supporting a modulatory role for NO, application of NO through administration of acid sodium nitrite evoked marked inhibitory effects on responses to transmural nerve stimulation. Substance P-like responses to nerve stimulation were abolished by substance P receptor antagonists and were enhanced by atropine, indicating a cholinergic influence on substance P-like neuroeffector transmission. Since acetylcholine can evoke release of NO from endothelium, the possible role of acetylcholine in NO release in ileum was examined. The release of NO/nitrite, determined by chemiluminescence, was inhibited by NG-monomethyl-L-arginine (L-NMMA), by calcium removal, by tetrodotoxin or by atropine, indicating a nerve-mediated control of NO production. A basis for the NO release is likely to be spontaneous neuronal activity, where release of acetylcholine, with subsequent muscarinic receptor activation, contributes to stimulation of NO formation.
Wiklund
C U
CU
Department of Physiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Wiklund
N P
NP
Gustafsson
L E
LE
D000109:Acetylcholine / Q000494:pharmacology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000502:physiology; D007498:Iris / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000502:physiology*; D013373:Substance P / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D019323:omega-N-Methylarginine
D009573:Nitrites; D011950:Receptors, Cholinergic; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001285:Atropine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine