Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum

Samara L. Freeman, Jorg Glatzle, Carla S. Robin, Melissa Valdellon, Catia Sternini, James W. Sharp, Helen E Raybould

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background & Aims: Release of 5-hydroxytryptamine (5-HT) from mucosal enterochromaffin cells and activation of 5-HT3 receptors (5-HT3Rs) on neurons in the gut wall is important in the response of the gut to the luminal environment. Intestinal inflammation is associated with increased levels of mucosal 5-HT. The aims of the study were to determine the following: (1) if 5-HT3R undergoes ligand-induced internalization in myenteric neurons, and (2) the effect of long-term increase of mucosal 5-HT on 5-HT3Rs. Methods: Acute effects of exogenous 5-HT or endogenous release of 5-HT by luminal glucose on cellular localization of 5-HT3Rs was determined by immunohistochemistry and confocal microscopy. Treatment with the serotonin re-uptake inhibitor, fluoxetine, for 6 days (20 mg/kg daily orally) was used to increase mucosal 5-HT chronically in rats. Net ileal fluid movement was measured in anesthetized rats by the weight change of a 2.5% agarose cylinder. Results: Acute increases in 5-HT induced by exogenous or endogenous 5-HT decreased 5-HT3R immunoreactivity at the neuronal cell membrane by 70% and 60%, respectively. Chronic fluoxetine treatment increased mucosal levels of 5-HT and decreased membrane 5-HT3R immunoreactivity by 27%. Net fluid absorption was decreased by a 5-HT3R agonist or by luminal glucose; this was attenuated 88% and 99%, respectively, by fluoxetine treatment. Conclusions: Long-term increase in 5-HT in the intestinal mucosa results in increased 5-HT3R internalization in myenteric neurons. Chronic changes in mucosal 5-HT may alter gastrointestinal secretory and motor function via ongoing loss of receptor from neuronal membrane, causing a mismatch between luminal content and absorption.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalGastroenterology
Volume131
Issue number1
DOIs
StatePublished - Jul 2006

ASJC Scopus subject areas

  • Gastroenterology

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    Freeman, S. L., Glatzle, J., Robin, C. S., Valdellon, M., Sternini, C., Sharp, J. W., & Raybould, H. E. (2006). Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum. Gastroenterology, 131(1), 97-107. https://doi.org/10.1053/j.gastro.2006.04.013