title: Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter.
abstract: 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.
authors.affiliation: Center for Swallowing and Motility Disorders, Brockton/West Roxbury Veterans Affairs Medical Center, Boston, Massachusetts 02132, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Kim
authors.forename: R K
authors.initials: RK
authors.lastname: Goyal
authors.forename: H
authors.initials: H
authors.lastname: Mashimo
mesh_terms: 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
chemical_list: 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