The arginine/nitric oxide pathway modulates sphincter of Oddi motor activity in guinea pigs and rabbits.
BACKGROUND
Nitric oxide acts as a neurotransmitter of nonadrenergic, noncholinergic pathways. The present study examined the role of the L-arginine/NO pathway on sphincter of Oddi motility.


METHODS
In anesthetized guinea pigs and rabbits, intracholedochal pressure was recorded by a perfused catheter whose open tip was maintained close to the sphincter of Oddi lumen. The contractile responses to cholecystokinin or bethanechol were recorded before and after treatment with either a specific NO synthetase inhibitor (NG-nitro-L-arginine methyl ester) or a donor of NO (sodium nitroprusside). The effect of NO synthase inhibition on isometric tension generated by muscle from rabbit sphincter of Oddi was tested in vitro.


RESULTS
Tonic pressure and phasic contractions significantly increased after NO synthase inhibition; responses to cholecystokinin and bethanechol were enhanced. In contrast, sodium nitroprusside reduced the response to cholecystokinin. Isolated muscle from rabbit sphincter of Oddi relaxed in response to the nicotinic agonist dimethyl-4-phenylpiperazinium. Relaxation was eliminated by either the neurotoxin tetrodotoxin or by NG-nitro-L-arginine methyl ester. NO synthase inhibition also suppressed the relaxatory response induced by electrical field stimulation. Calcium-dependent activity of NO synthase was detected in fresh homogenates from guinea pig and rabbit sphincter of Oddi tissue.


CONCLUSIONS
NO that is locally generated by a constitutive NO synthase regulates sphincter of Oddi motor function.
Mourelle
M
M
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Guarner
F
F
Moncada
S
S
Malagelada
J R
JR
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000502:physiology*
D009599:Nitroprusside; D009569:Nitric Oxide; D004246:Dimethylphenylpiperazinium Iodide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D012844:Sincalide; D019331:NG-Nitroarginine Methyl Ester