1. Distinguishing the contributions of neuronal and mucosal serotonin in the regulation of colonic motility.
- Author
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Martin AM, Jones LA, Wei L, Spencer NJ, Sanders KM, Ro S, and Keating DJ
- Subjects
- Animals, Colon, Enterochromaffin Cells, Fluoxetine pharmacology, Intestinal Mucosa, Mice, Serotonergic Neurons, Gastrointestinal Motility physiology, Serotonin pharmacology
- Abstract
Background: Specialized enterochromaffin (EC) cells within the mucosal lining of the gut synthesize and secrete almost all serotonin (5-hydroxytryptamine, 5-HT) in the body. Significantly lower amounts of 5-HT are made by other peripheral tissues and serotonergic neurons within the enteric nervous system (ENS). EC cells are in close proximity to 5-HT receptors in the ENS, and the role of 5-HT as a modulator of gut motility, particularly colonic motor complexes, has been well defined. However, the relative contribution of neuronal 5-HT to this process under resting and stimulus-evoked conditions is unclear., Methods: In this study, we combined the use of the selective serotonin transporter (SERT) inhibitor, fluoxetine, with two models of mucosal 5-HT depletion-surgical removal of the mucosa and our Tph1
Cre/ERT2 ; Rosa26DTA mouse line-to determine the relative contribution of neuronal and mucosal 5-HT to resting and distension-evoked colonic motility., Key Results: Fluoxetine significantly reduced the frequency of colonic migrating complexes (CMCs) in flat-sheet preparations with the mucosa present and in intact control Tph1-DTA colons in which EC cells were present. No such effect was observed in mucosa-free preparations or in intact Tph1-DTA preparations lacking EC cell 5-HT., Conclusions and Inferences: We demonstrate that mucosal 5-HT release plays an important role in distension-evoked colonic motility, and that SERT inhibition no longer alters gut motility when EC cells are absent, thus demonstrating that ENS 5-HT does not play a role in regulating gut motility., (© 2022 John Wiley & Sons Ltd.)- Published
- 2022
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