Editors' ChoiceSensory Perception

The sensitive cells in the gut

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Sci. Signal.  18 Jul 2017:
Vol. 10, Issue 488, eaao3888
DOI: 10.1126/scisignal.aao3888

Serotonin-producing enterochromaffin cells in the gut epithelium are chemosensors for the enteric nervous system.

The response of the enteric nervous system to dietary and microbial metabolites affects gastrointestinal activity. A cell type that has been proposed to be a chemosensor for the enteric nervous system is enterochromaffin cells, which constitute less than 1% of the gut epithelium but produce much of the total body serotonin, a regulator of gastrointestinal motility. To perform single-cell analysis, Bellono et al. generated intestinal organoids from mice that expressed a GFP reporter under the control of an enterochromaffin cell–specific promoter. GFP-positive enterochromaffin cells were electrically excitable, a property that was mediated by voltage-gated Na+ and Ca2+ channels. These cells produced Ca2+ responses when exposed to the chemical irritant allyl isothiocyanate (AITC; a compound found in wasabi), which activated the Ca2+-permeable channel TRPA1, and the microbial product isovalerate, which activated the olfactory receptor Olfr558. Various catecholamines, including epinephrine and norepinephrine, also induced Ca2+ responses in enterochromaffin cells. The use of pharmacological inhibitors revealed that these catecholamines activated the α2A-adrenergic receptor, which was localized to the basolateral surface and which resulted in the Gαi-mediated activation of the Ca2+-permeable channel TRPC4. Application of epinephrine, AITC, or isovalerate to the organoids induced Ca2+ responses in the enterochromaffin cells, which was followed by stimulation of a serotonin-activated ion channel reporter expressed in other cells in the organoids. In ex vivo colonic preparations, application of epinephrine or isovalerate to the epithelium evoked afferent activity. However, neither epinephrine nor isovalerate induced Ca2+ responses when directly applied to colonic sensory neurons. These results demonstrate that enterochromaffin cells are chemosensors for irritants, metabolites, and catecholamines (see also Beumer and Clevers).

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