What is the role of endogenous gut serotonin in the control of gastrointestinal motility?
Keating, Damien John
Spencer, Nicholas John
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In recent years, there have been dramatic changes in our understanding of the role of endogenous 5-Hydroxytryptamine (5-HT or serotonin) in the control of gastrointestinal (GI) motility. Whilst it is well accepted that there are numerous types of 5-HT receptors expressed on enteric neurons and that exogenous 5-HT potently stimulates GI-motility, understanding the role of endogenous 5-HT in GI-motility has been substantially more difficult to resolve. Recent studies found 5-HT3 and 5-HT4 antagonists have the same effects on peristalsis in colon preparations depleted of endogenous 5-HT. Then, recent work revealed that in mice with genetic mutations to prevent the synthesis of endogenous 5-HT from enterochromaffin EC) cells did not block major neurogenic motor patterns in the gut wall and did not reduce GI-transit in conscious animals, raising doubts about early hypotheses that endogenous 5-HT was critical for neurogenic GI-motility patterns. Indeed, functional evidence now suggests that 5-HT3 and 5-HT4 receptors on enteric nerves display constitutive activity. In summary, recent findings demonstrate that endogenous 5-HT released from the mucosa or enteric neurons is not required for the generation of major neurogenic motor patterns, at least in the large intestine, but that it likely acts as a modulator of contractile frequency. This review will discuss how and why our understanding of endogenous 5-HT has dramatically changed in the past few years.
© 2018 Elsevier Ltd. . This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policy