Article
"A nose in the gut": Olfactory receptors in the human gastrointestinal tract
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Published: | July 22, 2009 |
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Background: Chemoreceptors of the oral cavity and the nose analyze food prior to its uptake into the gastrointestinal tract. We investigated whether nasal olfactory receptors are also expressed by enterochromaffin (EC) cells of the human gut mucosa, and whether their ligands – odorants and spices – trigger a release of serotonin. Release of serotonin is the key event in the regulation of intestinal motility and secretion.
Methods: Expression of olfactory receptors was analyzed by RT PCR in human EC cells harvested by laser-assisted microdissection, in biopsies of the human small intestine, and in a carcinoid cell line (BON) derived from EC cells. Activation of EC cells by odorants was visualized by digital fluorescence imaging using the Ca2+ binding dye Fluo-4. Release of serotonin was measured in cell culture supernatants by serotonin ELISA, and by amperometry using carbon fibers directly placed on single cells.
Results: We found expression of four olfactory receptors (OR73, hOR17-7/11, OR1G1 [alias hOR17-209] und hOR17-210) in human EC cells, intestinal biopsies, and the BON cell line. Functional studies revealed that ligands of the identified olfactory receptors trigger a Ca2+ influx, elevation of intracellular Ca2+ levels, and, consequently, release of serotonin. Elevated intracellular Ca2+ levels were also found after depletion of intracellular Ca2+ stores by thapsigargin, but could be blocked by inhibitors of L-type Ca2+ channels (nifedipine), of phosholipase C (U73122), and of IP3 receptors (xestospongin C).
Conclusions: Intestinal olfactory receptors, influencing digestion and gut motility, and described in this study for the first time, could serve as possible new targets in the pharmacotherapy of intestinal diseases and motility disorders.