Distinguishing the contributions of neuronal and mucosal serotonin in the regulation of colonic motility

Alyce M. Martin, Lauren A. Jones, Lai Wei, Nick J. Spencer, Kenton M. Sanders, Seungil Ro, Damien J. Keating

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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 Tph1Cre/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.

Original languageEnglish
Article numbere14361
Number of pages6
JournalNeurogastroenterology and Motility
Issue number8
Early online date21 Mar 2022
Publication statusPublished - Aug 2022


  • enteric nervous system
  • enterochromaffin cells
  • fluoxetine
  • gastrointestinal motility
  • serotonin


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