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1 Gastrointestinal Disease Research Unit, Queen's University, Kingston, Ontario K7L 5G2; and 2 Department of Physiology and Biophysics, Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada
The efferent secretomotor activity
of capsaicin-sensitive nerves was monitored during the evolution of
2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis in the guinea
pig by recording changes in short-circuit current
(
Isc) in response to capsaicin, substance P
(SP), and carbachol. Submucosal-mucosal preparations mounted in
standard Ussing chambers were studied at time 0, at 8 h, and 1, 3, 5, 7, 14, and 30 days following the intraluminal
instillation of TNBS or saline. Maximal Isc
responses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated Isc were also significantly reduced. Similar
attenuation in capsaicin and carbachol responses was observed in
jejunal tissue 20 cm proximal to the inflamed site at day 7.
These studies demonstrate that efferent secretomotor function of
capsaicin-sensitive nerves is maintained early in TNBS ileitis but
significantly reduced by 24 h. By day 7, defects in
enterocyte secretory function at inflamed and noninflamed sites also
occurred, an effect that may be mediated by circulating cytokines.
capsaicin-sensitive nerves; submucosal neurons; substance P
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