Inhibition of neural nitric oxide synthase attenuates the chloride secretory response to stroking in human jejunum.
BACKGROUND
Stroking of human jejunal mucosa induces serotonin release and a rise in short-circuit current (DeltaI(sc)). Nitric oxide is known to function as a nonadrenergic, noncholinergic neurotransmitter in response to neural serotonin receptor activation in the rat. We hypothesize that neural nitrergic mechanisms mediate the chloride secretory response to mucosal stroking in human jejunum.


METHODS
Segments of normal proximal jejunum were obtained from patients having gastric bypass surgery for obesity. Muscle-stripped segments of jejunum were mounted in Ussing chambers under short-circuit conditions. The neural nitric oxide synthase inhibitor, l-thiocitrulline, was added to experimental tissues. Mucosal stroking of control and experimental segments was then performed.


RESULTS
Pretreatment with l-thiocitrulline attenuated the short circuit rise seen after stroking in the experimental group when compared with the control (5.4 +/- 1.5 microA/cm(2) vs 8.0 +/- 1.6 microA/cm(2); P <.05, Student t test, paired data, n = 11), but did not affect baseline I(sc) before stroking. Serotonin released by stroking was not different in experimental versus control tissue.


CONCLUSIONS
The significantly reduced DeltaI(sc) in the group pretreated with the neural nitric oxide synthase inhibitor suggests that nitric oxide liberated from enteric neurons participates in the chloride secretory response to stroking in human jejunum in vitro.
King
Brian N
BN
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298, USA.
Haque
Sheikh M
SM
Stoner
Michael C
MC
Ellis
Zach M
ZM
Kellum
John M
JM
D002712:Chlorides / Q000378:metabolism*; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007583:Jejunum / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010812:Physical Stimulation; D012701:Serotonin / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
D002712:Chlorides; D004791:Enzyme Inhibitors; C086715:thiocitrulline; D002956:Citrulline; D012701:Serotonin; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D013890:Thiourea