Increased Responsiveness of Rat Colonic Splanchnic Afferents to 5-ht After Inflammation and Recovery.
From: Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, Australia.
The Journal of physiology
- Publish Date: Feb 2007
- ISSN: 0022-3751
- Volume: 579
- Issue: Pt 1
- Pages: 203-13
- Medium: Print
- Language: English
- Citation (JAMA): Coldwell Jonathan R, Phillis Benjamin D, Sutherland Kate, et al. Increased Responsiveness of Rat Colonic Splanchnic Afferents to 5-ht After Inflammation and Recovery.. J. Physiol. (Lond.) Feb 2007;579:203-13
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(-4) m) 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 x 10(-6) to 8 x 10(-7) m in acute inflammation and recovered to 2 x 10(-6) m 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.
Mesh Headings (Keywords): Action Potentials, Afferent Pathways, Animals, Biological Markers, Calcitonin Gene-Related Peptide, Cell Degranulation, Colitis, Colon, Disease Models, Animal, Electrophysiology, Mast Cells, Nerve Fibers, Physical Stimulation, Rats, Rats, Sprague-Dawley, Recovery of Function, Serotonin, Splanchnic Nerves
Check for Full Text / PubMed Unique Identifier (PMID): 17138606
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