Role of the nitrergic pathway in motor effects of oxytocin in rat proximal colon. Issue 12 (14th June 2016)

• Record Type: Journal Article
• Authors: Wang, R.; Guo, L. Y.; Suo, M. Y.; Sun, Y.; Wu, J. Y.; Zhang, X. Y.; Liu, C. Y.
• Is Part Of: Neurogastroenterology & motility. Volume 28:Issue 12(2016)
• Page Start: 1815
• Page End: 1823
• Publication Date: 2016-06-14
• Subjects: colonic motility -- enteric nervous system -- gastrointestinal hormones -- nitric oxide -- oxytocin; Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12883
• Languages: English
• ISSNs: 1350-1925

Abstract

Abstract: 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. Key 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 N ω ‐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 & Inferences: 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. Abstract : In this study, we investigated whether the activation of oxytocin receptor (OTR) located on nitrergic neurons is involved in modulating colonic motor function through stimulation of nitric oxide (NO) release. The role of the nitrergic pathway in motor effects of oxytocin was assessed by organ bath experiments in vitro . Activation of OTR co‐expressed with neuronal nitric oxide synthase (nNOS) in myenteric neurons inhibits colonic spontaneous contraction and enhances electrically evoked nonadrenergic, noncholinergic (NANC) relaxation in longitudinal smooth muscle in vitro, which may be mediated through excitation of nitric oxide (NO) release from the myenteric nitrergic nerves.