Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery
- Jonathan R. Coldwell1,2,
- Benjamin D. Phillis1,
- Kate Sutherland1,2,
- Gordon S. Howarth2,4,5,6,7 and
- L. Ashley Blackshaw1,2,3
- 1Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia2Discipline of Physiology, 3Department of Medicine and 4Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia 5000, Australia5Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia6School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide, Australia7School of Biological Sciences, Flinders University, South Australia, Australia
- Corresponding author L. A. Blackshaw: Nerve-Gut Research Laboratory, Level 1, Hanson Institute, Frome Road, Adelaide, South Australia 5000, Australia. Email: ashley.blackshaw{at}adelaide.edu.au
Abstract
5-Hydroxytryptamine (5-HT) activates colonic splanchnic afferents, a mechanism by which it has been implicated in generating symptoms in postinfectious and postinflammatory states in humans. Here we compared mechanisms of colonic afferent activation by 5-HT and mechanical stimuli in normal and inflamed rat colon, and after recovery from inflammation. Colonic inflammation was induced in rats by dextran sulphate sodium. Single-fibre recordings of colonic lumbar splanchnic afferents revealed that 58% of endings responded to 5-HT (10−4m) in controls, 88% in acute inflammation (P < 0.05) and 75% after 21 days recovery (P < 0.05 versus control). Maximal responses to 5-HT were also larger, and the estimated EC50 was reduced from 3.2 × 10−6 to 8 × 10−7m in acute inflammation and recovered to 2 × 10−6m after recovery. Responsiveness to mechanical stimulation was unaffected. 5-HT3 receptor antagonism with alosetron reduced responses to 5-HT in controls but not during inflammation. Responses to the mast cell degranulator 48/80 mimicked those to 5-HT in inflamed tissue but not in controls, and more 5-HT-containing mast cells were seen close to calcitonin gene-related peptide-containing fibres in inflamed serosa. We conclude that colonic serosal and mesenteric endings exhibit increased sensitivity to 5-HT in inflammation, with both an increase in proportion of responders and an increase in sensitivity, which is maintained after healing of inflammation. This is associated with alterations in the roles of 5-HT3 receptors and mast cells.
Footnotes
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(Resubmitted 19 October 2006; accepted after revision 27 November 2006; first published online 30 November 2006)
- 2007 The Authors. Journal compilation © 2007 The Physiological Society
