Stroking human jejunal mucosa induces 5-HT release and  Cl<sup>−</sup> secretion via afferent neurons and 5-HT<sub>4</sub>receptors

Kellum, John M.; Albuquerque, Francisco; Stoner, Michael C.; Harris, Robert P.

doi:10.1152/ajpgi.1999.277.3.g515

Cited by 65 publications

(62 citation statements)

References 9 publications

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“…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).…”

Section: Taken Together Our Results Indicate That Trpa1 Acts As a Sementioning

confidence: 99%

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

Nozawa

Kawabata-Shoda

Doihara

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

315

323

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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 ...

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Section: Taken Together Our Results Indicate That Trpa1 Acts As a Sementioning

confidence: 99%

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

Nozawa

Kawabata-Shoda

Doihara

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

315

323

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“…It is unlikely that ondansetron stimulates secretion as data in both animals and man suggest to the contrary that they inhibit postprandial pancreatic and intestinal secretions. [18][19][20][21][22][23] We feel that it is more likely that the increase in fasting SBWC is due to reduced fasting small bowel motility. Ondansetron is known to inhibit colonic motility 24 and the MMC 25 at least in rodents.…”

Section: Discussionmentioning

confidence: 98%

Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

Marciani

Wright

Foley

et al. 2010

Aliment Pharmacol Ther

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SUMMARYBackground 5-HT 3 antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility.

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“…It is conceivable that the increase in colonic CgA in LC patients accounts for an increase in serotonin cells. Serotonin is thought to activate the submucosal sensory branch of the enteric nervous system and control, and accelerates gastrointestinal motility via interneurons and motor neurons (19,20). If this hypothesis were proven to be the case, diarrhoea, abdominal cramping and nausea symptoms could be explained on this basis.…”

Section: Discussionmentioning

confidence: 99%

High chromogranin A cell density in the colon of patients with lymphocytic colitis

Lomholt-Beck

GUNDERSEN²

2011

Mol Med Report

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Abstract. Microscopic colitis (MC) is a chronic condition that is characterized by watery diarrhoea with normal appearance of the colonic mucosa. MC is subdivided into two distinctive entities: lymphocytic colitis (LC) and collagenous colitis (CC). The etiology and pathophysiology of LC remain to be determined. The present study included 9 female patients with LC, with an average age of 34 years. Subjects (n=25) who underwent colonoscopy were used as controls. The subjects underwent colonoscopy due to gastrointestinal bleeding, where the source of bleeding was identified as haemorrhoids, or due to health concerns. The control subjects included 18 females and 7 males, with an average age of 49 years. Colonoscopy was performed in both patient and control groups, and biopsies were obtained from different segments of the colon. The biopsies were immunostained with the avidin-biotin complex method for human leucocytes CD45, collagen type III and chromogranin A (CgA). CgA was quantified by computer image analysis. The density of CgA-immunoreactive cells in patients with LC was significantly higher than that in controls. The high density of colonic CgA, a common marker for endocrine cells, indicates the possibility that colonic hormones are involved in the pathophysiology of LC. Serotonin-containing cells are the major endocrine cell type in the colon and constitute approximately 88% of the total endocrine cell population. It is likely that the increase in colonic CgA in LC patients accounts for an increase in serotonin cells. IntroductionMicroscopic colitis (MC) is a chronic condition, which is characterized by watery diarrhoea with normal appearance of the colonic mucosa. However, histopathological examinations of the colon revealed abnormal histology. This abnormality is of two distinctive types: lymphocytic colitis (LC) and collagenous colitis (CC). LC and CC exhibit colonic intraepithelial lymphocytosis, increase inflammatory cells within lamina propria and preserve crypt architecture. The incidence of LC has been reported to be 3.1/100,000 per year and the prevalence to be 14.4/100,000 (1,2).The etiology and pathophysiology of LC have yet to be determined. The symptoms of LC suggest an abnormally rapid intestinal motility and a decrease in absorption of water. The neuroendocrine system of the gut plays a significant role in regulating gut motility and absorption of water and salts (3-6). It is reasonable, therefore, to assume that the colonic endocrine cells may be affected and may be involved in the pathophysiology of this disorder.Chromogranin A (CgA) is a 68-kDa protein comprising 439 amino-acid residues, which was isolated for the first time from secretory granules of the bovine adrenal medulla (7,9). CgA is co-stored and co-released with monoamines and peptide hormones of the adrenal medulla, pituitary gland, parathyroid, thyroid C-cells, pancreatic islets, endocrine cells of the gastrointestinal tract and sympathetic nerves (7,8). The serum and tissue content of CgA serves as a marker for gut endocrine cell...

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Stroking human jejunal mucosa induces 5-HT release and Cl⁻ secretion via afferent neurons and 5-HT₄receptors

Cited by 65 publications

References 9 publications

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

High chromogranin A cell density in the colon of patients with lymphocytic colitis

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Stroking human jejunal mucosa induces 5-HT release and Cl− secretion via afferent neurons and 5-HT4receptors

Cited by 65 publications

References 9 publications

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

Effects of a 5‐HT3 antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

High chromogranin A cell density in the colon of patients with lymphocytic colitis

Contact Info

Product

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Stroking human jejunal mucosa induces 5-HT release and Cl⁻ secretion via afferent neurons and 5-HT₄receptors

Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging