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    Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation.

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    Publication date
    2007
    Author
    Dass, N.B.
    Bassil, A.K.
    North-Laidler, V.J.
    Morrow, R.
    Aziz, E.
    Tuladhar, Bishwa R.
    Sanger, G.J.
    Keyword
    Enteric nervous system
    Neuromedin U
    Prokinetic
    Motility
    Peristalsis
    NMU2R¿/¿
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    The neuromedin U (NMU) receptors, NMU1 and NMU2, are expressed in the gut but their functions are unclear. This study explores the role of NMU in gastrointestinal motility. Experimental approach: The effects of NMU were examined in the forestomach and colon isolated from NMU2R wild-type and NMU2R-/- (knockout) mice, looking for changes in muscle tension and in nerve-mediated responses evoked by electrical field stimulation (EFS), and in models of peristalsis in mouse colon and faecal pellet transit in guinea-pig colon. Key results: In the mouse forestomach, NMU (1 nM-10 ¿M) concentration-dependently induced muscle contraction, in the presence of tetrodotoxin and atropine, in preparations from both wild-type and NMU2R-/- mice (pEC50: 7.9, 7.6, Emax: 0.26, 0.20g tension, respectively, n=8 each concentration). The same concentrations of NMU had no consistent effects on the responses to EFS (n=8). In the mouse colon, NMU (0.1 nM-1 ¿M) had no significant effect on baseline muscle tension (n=8), but concentration-dependently potentiated EFS-evoked contractions in preparations from both wild-type and NMU2R-/- mice, pEC50: 8.1, 7.8, Emax: 24%, 21%, respectively, n=6-11. NMU (0.01 nM-0.1 ¿M, n=5-7) concentration-dependently decreased the interval between waves of peristalsis in the mouse colon (pEC50: 8.8) and increased the rate at which a faecal pellet moved along the guinea-pig colon. Conclusions and implications: These results demonstrate that NMU exerts colon-specific, nerve-mediated, prokinetic activity, via a pathway involving activation of NMU1 receptors. This suggests that this receptor may represent a molecular target for the treatment of intestinal motility disorders.
    URI
    http://hdl.handle.net/10454/3756
    Version
    No full-text available in the repository
    Citation
    Dass, N.B., Bassil, A.K., Tuladhar, B.R. and Sanger, G.J. et al (2007). Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation. British Journal of Pharmacology. Vol. 150, No. 4, pp. 502-508.
    Link to publisher’s version
    http://dx.doi.org/10.1038/sj.bjp.0707004
    Type
    Article
    Collections
    Life Sciences Publications

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