TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

Abstract

Serotonin (5-hydroxytryptamine; 5-HT) is abundantly present throughout the gastrointestinal tract and stored mostly in enterochromaffin (EC) cells, which are located on the mucosal surface. 5-HT released from EC cells stimulate both intrinsic and extrinsic nerves, which results in various physiological and pathophysiological responses, such as gastrointestinal contractions. EC cells are believed to have the ability to respond to the chemical composition of the luminal contents of the gut; however, the underlying molecular and cellular mechanisms have not been identified. Here, we demonstrate that the transient receptor potential (TRP) cation channel TRPA1, which is activated by pungent compounds or cold temperature, is highly expressed in EC cells. We also found that TRPA1 agonists, including allyl isothiocyanate and cinnamaldehyde, stimulate EC cell functions, such as increasing intracellular Ca 2؉ levels and 5-HT release, by using highly concentrated EC cell fractions and a model of EC cell function, the RIN14B cell line. Furthermore, we showed that allyl isothiocyanate promotes the contraction of isolated guinea pig ileum via the 5-HT 3 receptor. Taken together, our results indicate that TRPA1 acts as a sensor molecule for EC cells and may regulate gastrointestinal function.gastrointestinal tract ͉ RIN14B T he gastrointestinal tract has many functions, such as secretion, motility, and absorption. These functions are affected by various signals from the luminal contents, including nutrient and non-nutrient chemicals, mechanical factors, and microorganisms (1). The endocrine cells of the gut (hereafter enteroendocrine cells) are thought to be highly specialized mucosal cell subpopulations that receive luminal signals. There are more than 10 different types of enteroendocrine cells, and each type produces distinct transmitters/hormones (2). Serotonin (5-HT)-containing enterochromaffin (EC) cells, which are located throughout the gut, are considered to be the most prevalent enteroendocrine cells (3, 4). The 5-HT released from EC cells activate the submucosal sensory branch of the enteric nervous system and also control gastrointestinal motility and chloride secretion via interneurons and motor neurons (5, 6). Hence, EC cells are considered to be a major component of both the physiology and pathophysiology of gastrointestinal function (7,8). It has been suggested that EC cells respond to the contents of the lumen through the activation of receptor-operated or voltage-dependent Ca 2ϩ channels (9), however, the details of the cellular and molecular mechanisms have not yet been clarified.Many ion channels, like the transient receptor potential (TRP) channels expressed in sensory neurons, respond to natural compounds, especially spices and herbal medicines. For example, the vanilloid receptor (TRPV1) responds to the plant component capsaicin (the pungent ingredient in chili peppers), which produces the psychophysical sensation of heat or burning, whereas TRPM8 responds to menthol (found in peppermint), which produces ...

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

“…1). TRPV1 and transient receptor potential melastatin 8 (TRPM8) mRNA were not detected, although TRP ankyrin 1 (TRPA1) mRNA was detected in the whole intestine but not in LMMP or MCC, which is consistent with the observation of functional TRPA1 expression in enterochromaffin cells and the involvement of TRPA1 in murine intestinal contractions (Nozawa et al, 2009). …”

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TRP Channels in Visceral Pain

“…Enterochromaffin cells express TRPA1 and release serotonin in response to the TRPA1 agonist AITCl [73], which also releases CCK from other enteroendocrine (STC-1) cells [74]. These data suggest that dietary spices may augment release of mucosal mediators in response to nutrients.…”