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Modulation of peristalsis by NK3 receptor antagonism in guinea-pig isolated ileum is revealed as intraluminal pressure is raised

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1 NK3 tachykinin receptors mediate slow excitatory transmission in the enteric nervous system and play a role in reflexes induced by the intestinal stretch or mucosal compression. However, there is little evidence to suggest that these receptors are important in peristalsis. We have examined the effects of the NK3 receptor antagonist, talnetant, on peristalsis in guinea-pig isolated ileum induced by optimal and by supra-maximal distension pressures.

2 At the guinea-pig NK3 receptor, talnetant was shown to have high affinity (pKB 8.8) and selectivity over the guinea-pig NK1 and NK2 receptors.

3 Peristaltic waves in the ileum elicited by optimal distension pressures (1–3 cmH2O) were unaffected by talnetant at a supra-maximal concentration (250 nm).

4 Distension at a higher pressure (4 cmH2O) induced peristalsis in which there was incomplete closure of the lumen during each peristaltic wave and an increase in the periods of inactivity observed between bursts of peristaltic activity. The addition of talnetant (250 nm) increased the number of peristaltic events by reducing these periods of inactivity and thus, increased the productivity of the peristaltic reflex.

5 The data suggest that NK3 receptors are not involved in the modulation of peristaltic movements by physiological stimuli, but they may have a role in modulation of reflexes in extreme or pathological conditions.

Keywords: NK3; enteric nervous system; enteric reflexes; synaptic transmission; tachykinins

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2007.00396.x

Affiliations: 1: Neurology and Gastrointestinal-CEDD, GlaxoSmithKline, 3rd Avenue, Harlow, Essex CM19 5AW, UK 2: Department Pharmacology, School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK 3: Department Anatomy and Cell Biology, University of Melbourne, Victoria 3010, Australia

Publication date: April 1, 2007

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