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|Title:||Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery|
|Citation:||Journal of Physiology-London, 2007; 579(1):203-213|
|Publisher:||Blackwell Publishing Ltd|
|Jonathan R. Coldwell, Benjamin D. Phillis, Kate Sutherland, Gordon S. Howarth, and L. Ashley Blackshaw|
|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.|
|Keywords:||Colon; Afferent Pathways; Nerve Fibers; Splanchnic Nerves; Mast Cells; Animals; Rats; Rats, Sprague-Dawley; Colitis; Disease Models, Animal; Serotonin; Calcitonin Gene-Related Peptide; Physical Stimulation; Electrophysiology; Recovery of Function; Cell Degranulation; Action Potentials; Biomarkers|
|Appears in Collections:||Molecular and Biomedical Science publications|
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