Authors: D. C. E. Bulmer¹; W. Jiang¹; G. A. Hicks²; J. B. Davis²; W. J. Winchester²; D. Grundy¹

Source: Neurogastroenterology and Motility, Volume 17, Number 1, February 2005 , pp. 102-111(10)

Publisher: Wiley-Blackwell

Abstract:

A variety of inflammatory mediators and local metabolites, have been implicated in the sensitivity of intestinal afferent fibres to brief periods of ischaemia and reperfusion. As yet, the contribution of the vanilloid transient receptor potential (TRPV)1 receptor to the response to intestinal ischaemia remains undetermined. In the present study, the effect of pretreatment with the competitive TRPV1 antagonist capsazepine and the non-selective TRPV channel antagonist ruthenium red, on the mesenteric afferent fibre response to ischaemia was examined. In control animals there was a reproducible biphasic increase in whole nerve afferent fibre activity during two brief periods of ischaemia. Treatment with ruthenium red significantly attenuated the early phase increase in afferent fibre activity during ischaemia. However, capsazepine treatment did not significantly alter the afferent fibre response to either ischaemia or reperfusion. Further experiments in chronically vagotomized animals indicated that the early phase response to ischaemia was mediated via vagal afferent fibres. The mechanism via which ruthenium red selectively inhibited vagal afferent fibres during ischaemia is unknown, but it does not appear to involve blockade of the TRPV1 receptor.

Keywords: capsazepine; jejunal ischaemia; ruthenium red; spinal afferent fibres; vagal afferent fibres

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2004.00586.x

Affiliations: 1: Department of Biomedical Sciences, University of Sheffield, Sheffield, UK 2: Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, UK

Publication date: 2005-02-01

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