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

Mark Yeoman, Sara Fidalgo, Gianluca Marcelli, Bhavik Patel

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number10479 (2024)
JournalScientific Reports
Volume14
Issue number1
DOIs
Publication statusPublished - 7 May 2024

Keywords

  • Autoreceptors
  • Colon
  • Enterochromaffin cell
  • Ileum
  • Regulation
  • Serotonin
  • Transmitter

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