No / 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/3756 |
| Date | January 2007 |
| Creators | Dass, N.B., Bassil, A.K., North-Laidler, V.J., Morrow, R., Aziz, E., Tuladhar, Bishwa R., Sanger, G.J. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text in the repository |
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