Gastroenterology

Gastroenterology

Volume 132, Issue 5, May 2007, Pages 1890-1901
Gastroenterology

Basic–alimentary tract
Enterochromaffin Cells of the Human Gut: Sensors for Spices and Odorants

https://doi.org/10.1053/j.gastro.2007.02.036Get rights and content

Background & Aims: Release of serotonin from mucosal enterochromaffin cells triggered by luminal substances is the key event in the regulation of gut motility and secretion. We were interested to know whether nasal olfactory receptors are also expressed in the human gut mucosa by enterochromaffin cells and whether their ligands and odorants present in spices, fragrances, detergents, and cosmetics cause serotonin release. Methods: Receptor expression was studied by the reverse-transcription polymerase chain reaction method in human mucosal enterochromaffin cells isolated by laser microdissection and in a cell line derived from human enterochromaffin cells. Activation of the cells by odorants was investigated by digital fluorescence imaging using the fluorescent Ca2+ indicator Fluo-4. Serotonin release was measured in culture supernatants by a serotonin enzyme immunoassay and amperometry using carbon fiber microelectrodes placed on single cells. Results: We found expression of 4 olfactory receptors in microdissected human mucosal enterochromaffin cells and in a cell line derived from human enterochromaffin cells. Ca2+ imaging studies revealed that odorant ligands of the identified olfactory receptors cause Ca2+ influx, elevation of intracellular free Ca2+ levels, and, consequently, serotonin release. Conclusions: Our results show that odorants present in the luminal environment of the gut may stimulate serotonin release via olfactory receptors present in human enterochromaffin cells. Serotonin controls both gut motility and secretion and is implicated in pathologic conditions such as vomiting, diarrhea, and irritable bowel syndrome. Thus, olfactory receptors are potential novel targets for the treatment of gastrointestinal diseases and motility disorders.

Section snippets

Cell Culture

BON cells (a gift from Th. Seufferlein, University of Ulm, Germany) were cultured in Dulbecco’s modified Eagle medium (DMEM)/F-12 cell culture medium supplemented with 10% fetal calf serum (FCS) (both obtained from PAA Laboratories, Pasching, Austria) at 37°C in a 5% CO2 humidified atmosphere.

Laser Microdissection of Human EC Cells

Human EC cells were identified in sections by their immunoreactivity for vesicular monoamine transporter 1 (VMAT1)16 and subsequently cut out by laser microdissection.17 To minimize RNA degradation,

Expression of ORs in Human EC Cells

Odorants are detected by the large family of ORs that belong to the superfamily of G-protein-coupled receptors (GPCRs). Approximately 339 human genes are potential candidates for functional ORs.22, 23 An important property of ORs is that they display characteristic, partially overlapping ligand profiles. Thus, an odorant is detected by a combination of ORs. In this way, a multitude of odorants can be analyzed by a limited number of ORs.24, 25 At present, the ligand profiles for only a few human

Discussion

Previous investigations have shown that gastrointestinal EC cells act as sensors responding to mechanical stimulation or to nutrients, such as glucose and fatty acids, with secretion of serotonin.5, 9, 10, 11, 12, 13 The present study shows that, in addition, odorants trigger release of serotonin, which stimulates the submucosal sensory branch of the enteric nervous system,38, 39 and, via inter- and motorneurons, control gut motility and chloride secretion by enterocytes.4, 5, 6 Abnormalities

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    Parts of this work originated within Thomas Braun’s doctoral thesis at the Medical Faculty of the Ludwig Maximilian University Munich.

    Supported by Graduate School 333 (Biology of Human Diseases) by a predoctoral research fellowship of the Deutsche Forschungsgemeinschaft (to T.B.).

    1

    T.B. and P.V. contributed equally to this work.

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