Role of the nitrergic pathway in motor effects of oxytocin in rat proximal colon.
BACKGROUND
Oxytocin (OT) reduces rat duodenal tone and mouse intestinal transit; however, the underlying mechanisms are not totally understood. Consequently, this study was designed to investigate the influence of OT on spontaneous mechanical activity and neurally evoked responses, to characterize the mechanisms of the action, and to determine the distribution of the OT receptor (OTR) in rat proximal colonic muscle strips.


METHODS
The organ bath technique with electrical field stimulation, western blotting, and immunofluorescence were used.


RESULTS
In rat proximal colon, exogenous OT induced a concentration-dependent reduction of the spontaneous mechanical activity without affecting the resting basal tone, which was abolished by atosiban, an OTR antagonist, by tetrodotoxin (TTX), a neural blocker or by Nω-propyl-l-arginine hydrochloride, an inhibitor of neuronal nitric oxide synthase (nNOS). The inhibitory effects of OT were not affected by atropine or the vasoactive intestinal peptide (VIP) receptor antagonist [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (VIPHyb). Proximal colon responses to electrical field stimulation were characterized by nonadrenergic, noncholinergic (NANC) relaxation, which was followed by an off-contraction. Oxytocin enhanced only NANC relaxation. Oxytocin stimulated spontaneous NO release from the longitudinal muscle myenteric plexus preparation of rat proximal colon. Western blot and immunohistochemistry experiments showing the presence of the OTR in proximal colon, and its co-localization with nNOS established that myenteric nitrergic neurons express OTR.


CONCLUSIONS
The activation of OTR located on nitrergic neurons may negatively modulate colonic spontaneous contraction and enhance electrically evoked NANC relaxation through excitation of NO release.
Department of Physiology, Shandong University School of Medicine, Jinan, China.
R
R
Wang
Department of Physiology, Shandong University School of Medicine, Jinan, China.
L Y
LY
Guo
Department of Physiology, Shandong University School of Medicine, Jinan, China.
M Y
MY
Suo
Department of Physiology, Shandong University School of Medicine, Jinan, China.
Y
Y
Sun
Department of Physiology, Shandong University School of Medicine, Jinan, China.
J Y
JY
Wu
Department of Genetics, Shandong University School of Medicine, Jinan, China.
X Y
XY
Zhang
Department of Physiology, Shandong University School of Medicine, Jinan, China.
C Y
CY
Liu
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000819:agonists / Q000502:physiology*
D018045:Receptors, Oxytocin; D009569:Nitric Oxide; D010121:Oxytocin
colonic motility; enteric nervous system; gastrointestinal hormones; nitric oxide; oxytocin