Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs.
OBJECTIVE
Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO).


METHODS
Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time.


RESULTS
CCK-8 decreased the phasic wave amplitude of the choledochal sphincter, and increased NO release. N(G)-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, increased the spontaneous motility and converted the CCK-induced inhibitory response into an excitatory response. L-NAME also reduced NO release and abolished the increase of NO that had been caused by CCK-8. These effects were reduced by treatment with L-arginine (L-Arg). L-Arg application enhanced NO release, and recovered the increase of NO by CCK-8.


CONCLUSIONS
These studies demonstrate that CCK relaxes the choledochal sphincter and this relaxant response is mediated by NO.
Shima
Y
Y
First Department of Surgery, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Okayama, Japan.
Mori
M
M
Takakura
N
N
Tanaka
N
N
Yokoi
I
I
Kabuto
H
H
Yamazato
T
T
D000818:Animals; D003135:Common Bile Duct / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D004195:Disease Models, Animal; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008991:Monitoring, Physiologic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology / Q000502:physiology*; D009803:Sphincter of Oddi / Q000187:drug effects / Q000502:physiology*
D005765:Gastrointestinal Agents; D009569:Nitric Oxide; D012844:Sincalide; D019331:NG-Nitroarginine Methyl Ester