Enterochromaffin cells of the human gut: sensors for spices and odorants.
OBJECTIVE
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 Ca(2+) 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. Ca(2+) imaging studies revealed that odorant ligands of the identified olfactory receptors cause Ca(2+) influx, elevation of intracellular free Ca(2+) 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.
Braun
Thomas
T
Institute of Anatomy, Ludwig Maximilian University Munich, Munich, Germany.
Voland
Petra
P
Kunz
Lars
L
Prinz
Christian
C
Gratzl
Manfred
M
D000814:Aniline Compounds; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004759:Enterochromaffin Cells / Q000502:physiology*; D005456:Fluorescent Dyes; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009812:Odorants; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017365:Spices; D014966:Xanthenes
D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D018035:Receptors, Odorant; D014966:Xanthenes; D012701:Serotonin; D002118:Calcium