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Amperometry approach curve profiling to understand the regulatory mechanisms governing the concentration of intestinal extracellular serotonin

Yeoman, Mark S., Fidalgo, Sara, Marcelli, Gianluca, Patel, Bhavik Anil (2024) Amperometry approach curve profiling to understand the regulatory mechanisms governing the concentration of intestinal extracellular serotonin. Scientific Reports, 14 (1). Article Number 10479. ISSN 2045-2322. (doi:10.1038/s41598-024-61296-9) (KAR id:105877)

Abstract

Enterochromaffin (EC) cells located within the intestinal mucosal epithelium release serotonin (5-HT) to regulate motility tones, barrier function and the immune system. Electroanalytical methodologies have been able to monitor steady state basal extracellular 5-HT levels but are unable to provide insight into how these levels are influenced by key regulatory processes such as release and uptake. We established a new measurement approach, amperometry approach curve profiling, which monitors the extracellular 5-HT level at different electrode–tissue (E–T) distances. Analysis of the current profile can provide information on contributions of regulatory components on the observed extracellular 5-HT level. Measurements were conducted from ex vivo murine ileum and colon using a boron-doped diamond (BDD) microelectrode. Amperometry approach curve profiling coupled with classical pharmacology demonstrated that extracellular 5-HT levels were significantly lower in the colon when compared to the ileum. This difference was due to a greater degree of activity of the 5-HT transporter (SERT) and a reduced amount of 5-HT released from colonic EC cells. The presence of an inhibitory 5-HT4 autoreceptor was observed in the colon, where a 40% increase in extracellular 5-HT was the half maximal inhibitory concentration for activation of the autoreceptor. This novel electroanalytical approach allows estimates of release and re-uptake and their contribution to 5-HT extracellular concentration from intestinal tissue be obtained from a single series of measurements.

Item Type: Article
DOI/Identification number: 10.1038/s41598-024-61296-9
Uncontrolled keywords: Colon, Serotonin, Enterochromaffin cell, Autoreceptors, Transmitter, Regulation, Ileum
Subjects: Q Science
Divisions: Divisions > Division of Computing, Engineering and Mathematical Sciences > School of Engineering and Digital Arts
Funders: Engineering and Physical Sciences Research Council (https://ror.org/0439y7842)
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 10 May 2024 12:48 UTC
Last Modified: 05 Nov 2024 13:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/105877 (The current URI for this page, for reference purposes)

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