Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter.
To identify the enzymatic source of nitric oxide (NO) in the lower esophageal sphincter (LES), studies were performed in wild-type and genetically engineered endothelial nitric oxide synthase [eNOS(-)] and neuronal NOS [nNOS(-)] mice. Under nonadrenergic noncholinergic (NANC) conditions, LES ring preparations developed spontaneous tone in all animals. In the wild-type mice, electrical field stimulation produced frequency-dependent intrastimulus relaxation and a poststimulus rebound contraction. NOS inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM) abolished intrastimulus relaxation and rebound contraction. In nNOS(-) mice, both the intrastimulus relaxation and rebound contraction were absent. However, in eNOS(-) mice there was no significant difference in either the relaxation or rebound contraction from the wild-type animal. Both nNOS(-) and eNOS(-) tissues showed concentration-dependent relaxation to NO donor diethylenetriamine-NO and there was no difference in the sensitivity to the NO donor in nNOS(-), eNOS(-), or wild-type animals. These results indicate that in mouse LES, nNOS rather than eNOS is the enzymatic source of the NO that mediates NANC relaxation and rebound contraction.
Kim
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Center for Swallowing and Motility Disorders, Brockton/West Roxbury Veterans Affairs Medical Center, Boston, Massachusetts 02132, USA.
Goyal
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Mashimo
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D000818:Animals; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D018377:Neurotransmitter Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse