The effect of peroxynitrite on sphincter of Oddi motility.
BACKGROUND
Nitric oxide (NO*) is an inhibitory neurotransmitter that induces sphincter of Oddi relaxation. Superoxide (O*-2)-scavenging enzymes are present in enteric plexuses of the sphincter of Oddi and O*-2 alters sphincter of Oddi motor function. O*-2 rapidly oxidizes nitric oxide (NO*) to form peroxynitrite (ONOO-), thus terminating the biological activity of NO*. The aim of our study was to determine the effects of ONOO- on sphincter of Oddi motility in vitro.


METHODS
Adult opossums were sacrificed and the sphincter of Oddi was removed and placed in a tissue bath containing oxygenated Krebs solution at 37 degreesC. In the first series of experiments, force transducers recorded tension in a transverse orientation at two sites along the spontaneously contracting sphincter of Oddi. In a second series of experiments, circular muscle strips were precontracted with carbachol and stimulated by an electrical field.


RESULTS
ONOO-, superoxide dismutase (SOD), Nomega-nitro-l-arginine (l-NNA), or oxyhemoglobin were added to the tissue baths. ONOO- decreased the frequency of contractions in the spontaneously contracting sphincter of Oddi. Adding hemoglobin increased the frequency of contractions. ONOO- also increased the stimulation-induced relaxation compared to controls. The increase in relaxation induced by ONOO- was inhibited by oxyhemoglobin and l-NNA but not SOD. Pretreatment with oxyhemoglobin prevented the increase in the stimulation-induced relaxation caused by ONOO-.


CONCLUSIONS
These results suggest that hemoglobin binds ONOO- or that ONOO- generates NO.
Herrmann
B W
BW
Departments of Surgery and Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA.
Cullen
J J
JJ
Ledlow
A
A
Murray
J A
JA
Conklin
J L
JL
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009566:Nitrates / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009893:Opossums; D010108:Oxyhemoglobins / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009566:Nitrates; D010108:Oxyhemoglobins; D019335:Nitroarginine; C039642:peroxynitric acid; D002217:Carbachol; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase