Effect of peroxynitrite on motor function of the opossum esophagus.
Nitric oxide (NO*) is a mediator of esophageal motility. Esophageal dysmotility accompanies esophagitis. During inflammation, superoxide and NO* form peroxynitrite (ONOO-), a reactive molecule that alters cellular function. We tested the hypotheses that ONOO- affects esophageal motility and is produced in association with esophagitis. Transverse muscle strips from the opossum esophagus were stimulated by an electrical field, and nitrotyrosine immunoblots were performed. Peroxynitrite, its decomposed form, or NaNO2 relaxed the lower esophageal sphincter (LES) and attenuated the off response. These effects were inhibited by oxyhemoglobin (Hgb). An antagonist of guanylate cyclase, 1H[1,2,4]oxadiazole[4,3]quinoxalin-1-one (ODQ), inhibited the LES relaxation produced by ONOO-. Nitrotyrosine, a footprint for ONOO- production, was detected in inflamed esophagus. These studies support the hypotheses that ONOO alters esophageal motor function and is formed in association with esophagitis. It is possible that some of the esophageal motor dysfunction seen with esophagitis may be related to the formation of ONOO-.
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 55242, USA.
Murray
J A
JA
Kooy
N
N
Conklin
J L
JL
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004941:Esophagitis / Q000378:metabolism*; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D009893:Opossums; D010069:Oxadiazoles / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D010108:Oxyhemoglobins / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009566:Nitrates; D010069:Oxadiazoles; D016877:Oxidants; D010108:Oxyhemoglobins; D011810:Quinoxalines; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D006162:Guanylate Cyclase