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Am J Physiol Gastrointest Liver Physiol 282: G972-G980, 2002. First published December 19, 2001; doi:10.1152/ajpgi.00037.2001
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Vol. 282, Issue 6, G972-G980, June 2002

Alterations in capsaicin-evoked electrolyte transport during the evolution of guinea pig TNBS ileitis

Paula Miceli1, Gerald P. Morris1, Wallace K. MacNaughton2, and Stephen Vanner1

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 (Delta 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 Delta Isc responses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated Delta 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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