Abstract
The afferent innervation of the gastrointestinal (GI) tract consists of intrinsic
and extrinsic sensory neurons that respond to nutrients, chemicals or mechanical stimuli
within the gut lumen. Most stimuli do not interact directly with the afferent nerves
but instead activate specialised cells in the epithelium in a process of sensory transduction.
It is thought that one of the first steps in this process is the release of serotonin
(5-HT) from the enterochromaffin (EC) cells. The EC cells are a sub-type of enteroendocrine
(EE) cells which are found among the enterocytes of the intestinal epithelium. The
EC cells are responsible for the production and storage of the largest pool of 5 HT
in the body. Released 5-HT can act on the intrinsic nerves and vagal endings. This
review will focus on the role of 5-HT in sensory transduction and examine how the
EC cell produces and releases 5-HT. We will explore recent developments that have
helped to elucidate some of the proteins that allow EC cells to sense the luminal
environment. Finally, we will highlight some of the findings from new studies using
electrochemical techniques which allow the real-time recording of 5-HT concentrations
near to the EC cell.
Abbreviations:
GI (gastrointestinal), ENS (enteric nervous system), CCK (cholecystokinin), ATP (adenosine-5′-triphosphate), EC (enterochromaffin cell), EE (enteroendocrine cell), UC (ulcerative colitis), IBS (irritable bowel syndrome), IBD (inflammatory bowel disease), 5-hydroxytryptamine or 5-HT (serotonin), SERT (serotonin reuptake transporter), TpH (tryptophan hydroxylase), 5-HTP (5-hydroxytryptophan), 5-HIAA (5-hydroxyindoleacetic acid), CGA (chromogranin A), GABA (gamma-aminobutyric acid), SST (somatostatin)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Autonomic Neuroscience: Basic and ClinicalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- On the presence of serotonin in the gut lumen and possible release mechanisms.Acta Physiol. Scand. 1981; 112: 263-269
- Substance P and 5-HT in granules isolated from an intestinal argentaffin carcinoid.Histochemistry. 1977; 52: 217-222
- Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain.BMC biotechnol. 2009; 9: 23
- ATP and sensory transduction in the enteric nervous system.Neuroscientist. 2003; 9: 243-260
- Real-time detection of serotonin release from enterochromaffin cells of the guinea pig ileum.Neurogastroenterol. Motil. 2004; 16: 511-514
- Real-time measurement of serotonin release and motility in guinea pig ileum.J. Physiol. 2006; 577: 689-704
- Real-time release of serotonin from mouse ileum.Gastroenterology. 2006; 130: A256
- The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors.Neuroscientist. 2000; 101: 459-469
- Inflammation-induced increases in the release and uptake of serotonin in mouse colon.Fundam. Clin. Pharmacol. 2008; 22: 121
- Characterisation of serotonin release from human colonic mucosa using real-time electrochemistry.Neurogastroenterol. Motil. 2008; 20: 43
- Serotonin (5-HT) release and uptake measured by real-time electrochemical techniques in the rat ileum.Am. J. Physiol. 2008; 295: G1228-G1236
- Intestinal serotonin signalling measured in high-fat diet rats using electrochemical techniques.Neurogastroenterol. Motil. 2008; 20: 23
- Enhanced serotonin release and uptake in DSS-treated mouse colon.Neurogastroenterol. Motil. 2008; 20: 63
- Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells.Chem. Senses. 2007; 32: 41-49
- High mucosal serotonin availability in neonatal guinea pig ileum is associated with low serotonin transporter expression.Gastroenterology. 2007; 132: 2438-2447
- Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2, 4, 6-trinitrobenzene sulfonic acid colitis in mice.Am. J. Physiol. Gastrointest. Liver Physiol. 2009; 296: G685-G695
- Sensory transmission in the gastrointestinal tract.Neurogastroenterol. Motil. 2007; 19: 1-19
- 5-Hydroxytryptamine and enterochromaffin cells in the irritable bowel syndrome.in: Gastroenterology. 2000: 479
- Enterochromaffin cells of the human gut: sensors for spices and odorants.Gastroenterology. 2007; 132: 1890-1901
- Gastrointestinal melatonin: localization, function, and clinical relevance.Dig. Dis. Sci. 2002; 47: 2336-2348
- The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa.J. Physiol. 1959; 146: 18-28
- The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity.J. Physiol. 1958; 140: 381-407
- Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome.Gastroenterology. 2002; 123: 425-432
- Enterochromaffin (EC-) cells of the mammalian gastro-entero-pancreatic (GEP) endocrine system: cellular source of pro-dynorphin-derived peptides.Cell Tissue Res. 1988; 253: 173-179
- Enterochromaffin cells of the digestive system: cellular source of guanylin, a guanylate cyclase-activating peptide.Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 2935-2939
- Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception.Am. J. Physiol. 1998; 275: G433-G448
- Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells.Nature. 1992; 356: 60-63
- Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model.Gastroenterology. 2004; 127: 188-202
- Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology. 2004; 126: 1657-1664
- 5-HT activates neural reflexes regulating secretion in the guinea-pig colon.Neurogastroenterol. Motil. 1997; 9: 181-186
- Activation of 5-HT1P receptors on submucosal afferents subsequently triggers VIP neurons and chloride secretion in the guinea-pig colon.JANS. 1997; 66: 105-110
- WE-14, a chromogranin a-derived neuropeptide.Ann. N. Y. Acad. Sci. 2002; 971: 311-316
- Transport mechanisms governing serotonin clearance in vivo revealed by high-speed chronoamperometry.J. Neurosci. Methods. 2005; 143: 49-62
- QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells.Mol. Cell. Biochem. 2009; https://doi.org/10.1007/s11010-11009-10165-11017
- Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.Clin. Gastroenterol. Hepatol. 2005; 3: 349-357
- Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells.Biochem. Soc. Trans. 2005; 33: 302-305
- Intestinal glucose sensing and regulation of intestinal glucose absorption.Biochem. Soc. Trans. 2007; 35: 1191-1194
- Histochemical localization of monoamine oxidase in whole-body, freeze-dried sections of mice.Histochem. J. 1984; 16: 919-929
- Colonic endocrine cells in inflammatory bowel disease.J. Intern. Med. 1997; 242: 413-419
- The pharmacology of indolealkylamines.Pharmacol. Rev. 1954; 6: 425-487
- The human carcinoid cell line. BON. A model system for the study of carcinoid tumors.Ann. N. Y. Acad. Sci. 1994; 733: 393-406
- Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract.Gastroenterology. 1985; 89: 1366-1373
- Cholinergic agonists induce vectorial release of serotonin from duodenal enterochromaffin cells.Science. 1982; 217: 355-356
- Regulation of serotonin release from rabbit intestinal enterochromaffin cells.J. Pharmacol. Exp. Ther. 1983; 227: 755-766
- Differential demonstration of the motilin-cell and the enterochromaffin-cell.Scand. J. Gastroenterol. Suppl. 1976; 39: 43-45
- Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine.Gastroenterology. 1996; 111: 1281-1290
- Immuno-electron microscopic study of differential localization of motilin and serotonin in the rabbit duodenal epithelium.Peptides. 1998; 19: 65-73
- Effect of VIP and PACAP on vascular and luminal release of serotonin from isolated perfused rat duodenum.Ann. N.Y. Acad. Sci. 1998; 865: 495-502
- Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003; 284: R1269-R1276
- Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses.Am. J. Physiol. 1999; 277: G922-G928
- Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine.Naunyn Schmiedebergs Arch. Pharmacol. 1993; 347: 137-140
- Nafion-coated electrodes with high selectivity for CNS electrochemistry.Brain Res. 1984; 290: 390-395
- Review article: serotonin receptors and transporters—roles in normal and abnormal gastrointestinal motility.Aliment. Pharmacol. Ther. 2004; 20: 3-14
- The serotonin signaling system: from basic understanding to drug development for functional GI disorders.Gastroenterology. 2007; 132: 397-414
- 5-Hydroxytryptamine and enteric neurones.in: Fozard J.R. The Peripheral Actions of 5-HT. Oxford Medical Publications, Oxford1989: 247-273
- Function, expression, and characterization of the serotonin transporter in the native human intestine.Am. J. Physiol. Gastrointest. Liver Physiol. 2008; 294: G254-G262
- Melatonin treatment reverts age-related changes in guinea pig gallbladder neuromuscular transmission and contractility.J. Pharmacol. Exp. Ther. 2006; 319: 847-856
- 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons.Am. J. Physiol. 1996; 270: G778-G782
- 5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine.Gastroenterology. 1998; 115: 370-380
- Silver stains demonstrating neuroendocrine cells.Biotech. Histochem. 2004; 79: 37-44
- 5-HT system in the gut: roles in the regulation of visceral sensitivity and motor functions.Eur. Rev. Med. Pharmacol. Sci. 2008; 12: 63-67
- Enteric nervous system.Curr. Opin. Gastroenterol. 2005; 21: 176-182
- Amine mechanisms in enterochromaffin and enterochromaffin-like cells of gastric mucosa in various mammals.Histochem. Histochem. 1970; 21: 189-220
- A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells.Histochem. Cell Biol. 2007; 128: 457-471
- Enterochromaffin cells as the endocrine source of gastrointestinal substance P.Histochemistry. 1976; 49: 343-347
- Direct and indirect actions of 5-hydroxytryptamine on the discharge of mesenteric afferent fibres innervating the rat jejunum.J. Physiol. 1998; 506: 551-561
- Chemosensory perception in the gut.News Physiol. Sci. 1999; 14: 18-23
- Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors.Pharmacol. Exp. Ther. 1999; 288: 93-97
- Participation of 5-HT3, 5-HT4, and nicotinic receptors in the peristaltic reflex of guinea pig distal colon.Am. J. Physiol. 1996; 271: G849-G857
- Afferent hypersensitivity in a mouse model of post-inflammatory gut dysfunction: role of altered serotonin metabolism.J. Physiol. 2008; 586: 4517-4530
- Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells.Am. J. Physiol. 2006; 291: G778-G791
- GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR.Physiol. Genomics. 2007; 30: 363-370
- Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants.Am. J. Physiol. Gastrointest. Liver Physiol. 2008; 295: G260-G272
- d-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells.Gastroenterology. 2001; 121: 1400-1406
- Mechanical stimulation activates Galphaq signaling pathways and 5-hydroxytryptamine release from human carcinoid BON cells.J Clin Invest. 2001; 108: 1051-1059
- Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity.J. Neurosci. 1992; 12: 235-248
- In situ identification and visualization of neurons that mediate enteric and enteropancreatic reflexes.J. Comp. Neurol. 1996; 371: 270-286
- Receptors and transmission in the brain-gut axis: potential for novel therapies. I. Receptors on visceral afferents.Am. J. Physiol. 2001; 280: G787-G794
- Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis.Am. J. Physiol. Gastrointest. Liver Physiol. 2003; 285: G207-G216
- Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis.Neurogastroenterol. Motil. 2005; 17: 565-574
- Evidence for a distinct mechanism of serotonin transporter gene regulation in the human intestine involving a novel splice variant.Gastroenterology. 2005; 128: A59
- Novel promoter and alternate transcription start site of the human serotonin reuptake transporter in intestinal mucosa.Neurogastroenterol. Motil. 2009; 21: 534-541
- Identification and characterization of glucoresponsive neurons in the enteric nervous system.J. Neurosci. 1999; 19: 10305-10317
- l-Type calcium channels in enterochromaffin cells from guinea pig and human duodenal crypts: an in situ study.Gastroenterology. 1999; 117: 1363-1369
- Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits.Auton. Neurosci. 2006; 126–127: 250-257
- 5-Hydroxytryptamine, enterotoxins, and intestinal fluid secretion.Gastroenterology. 1998; 115: 1009-1012
- Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2.J. Physiol. 2007; 582: 379-392
- An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine.J. Physiol. 2009; 587: 195-210
- Uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells occurs through the neuronal serotonin transporter (SERT).J. Pharmacol. Exp. Ther. 2003; 306: 355-362
- Review article: intestinal serotonin signalling in irritable bowel syndrome.Aliment. Pharmacol. Ther. 2006; 23: 1067-1076
- Carcinoid tumors and syndrome.Gastroenterol. Nurs. 2002; 25: 105-111
- The functional characterization of normal and neoplastic human enterochromaffin cells.J. Clin. Endocrinol. Metab. 2006; 91: 2340-2348
- ATP and 5-HT are principal neurotransmitters in the descending excitatory reflex pathway of the guinea-pig ileum.Neurogastroenterol. Motil. 2002; 14: 255-264
- Slow excitatory post-synaptic potentials in myenteric AH neurons of the guinea-pig ileum are reduced by the 5-hydroxytrytamine7 receptor antagonist SB 269970.Neuroscientist. 2005; 134: 975-986
- The crucial role of chromogranins in storage and exocytosis revealed using chromaffin cells from chromogranin A null mouse.J. Neurosci. 2008; 28: 3350-3358
- Enterochromaffin cell and 5-hydroxytryptamine responses to the same infectious agent differ in Th1 and Th2 dominant environments.Gut. 2008; 57: 475-481
- Bipolarity of duodenal enterochromaffin cells in the rat.Cell Tissue Res. 1987; 248: 49-54
- TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells.Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 3408-3413
- PACAP regulation of secretion and proliferation of pure populations of gastric ECL cells.J. Mol. Neurosci. 2005; 26: 85-97
- Proliferative capacity of enterochromaffin cells in guinea-pigs with experimental ileitis.Cell Tissue Res. 2007; 329: 433-441
- Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis.Am. J. Physiol. Gastrointest. Liver Physiol. 2004; 287: G998-G1007
- Immunoelectron microscopic study of the luminal release of chromogranin A from rat enterochromaffin cells.Histochem. Cell Biol. 1999; 111: 253-257
- Gamma-aminobutyric acid immunoreactivity in the enterochromaffin cells of the rat stomach.Acta Anat. (Basel). 1992; 145: 127-131
- Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine.J. Neurosci. 2000; 20: 3295-3309
- Continuous amperometric detection of co-released serotonin and melatonin from the mucosa in the ileum.Analyst. 2008; 133: 516-524
- In vitro continuous amperometric monitoring of 5-hydroxytryptamine release from enterochromaffin cells of the guinea pig ileum.Analyst. 2007; 132: 41-47
- Enterochromaffin cells of the mammalian small intestine as the source of motilin.Virchows Arch. B Cell Pathol. 1974; 16: 111-120
- Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal tract.Gastroenterology. 1997; 113: 1007-1014
- Evidence for serotonergic system involvement in the effect of morphine on gastrointestinal motility in the rat.Gen. Pharmacol. 1995; 26: 779-783
- Regulation of 5-HT release from enterochromaffin cells.Behav. Brain Res. 1996; 73: 83-87
- Visceral perception: sensory transduction in visceral afferents and nutrients.Gut. 2002; 51: i11-i14
- Sensory mechanisms: transmitters, modulators and reflexes.Neurogastroenterol. Motil. 2004; 16: 60-63
- Glucose sensing in L cells: a primary cell study.Cell Metab. 2008; 8: 532-539
- The “normal” endocrine cell of the gut: changing concepts and new evidences.Ann. N.Y. Acad. Sci. 2004; 1014: 1-12
- Cellular localization of monoamine oxidase A and B in human tissues outside of the central nervous system.Cell Tissue Res. 2001; 304: 215-220
- Taste receptor signaling in the mammalian gut.Curr. Opin. Pharmacol. 2007; 7: 557-562
- Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 16767-16772
- New antiemetic drugs.Can. J. Physiol. Pharmacol. 1990; 68: 314-324
- Carbamylcholine- and catecholamine-induced intracellular calcium dynamics of epithelial cells in mouse ileal crypts.Gastroenterology. 1995; 108: 1345-1356
- Effects of AIF4- and ATP on intracellular calcium dynamics of crypt epithelial cells in mouse small intestine.Cell Tissue Res. 1999; 298: 295-305
- Identification of a vesicular nucleotide transporter.Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 5683-5686
- Isolation and receptor profiling of ileal enterochromaffin cells.Acta Physiol. Scand. 2004; 182: 53-62
- Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response.Pharmacogenomics J. 2003; 3: 64-66
- The tachykinin peptide family.Pharmacol. Rev. 2002; 54: 285-322
- KRJ-I and BON cell lines: defining an appropriate enterochromaffin cell neuroendocrine tumor model.Neuroendocrinology. 2009; 89: 458-470
- Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion.Am. J. Physiol. 1995; 269: G346-G351
- Substance P like-immunoreactivity release from enterochromaffin cells of rat caecum mucosa. Inhibition by serotonin and calcium-free medium.Neurochem. Int. 1992; 20: 529-536
- Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion.J. Pineal Res. 2003; 34: 288-293
- Endocrine cells in human intestine: an immunocytochemical study.Gastroenterology. 1983; 85: 1120-1130
- Human colonic substance P-producing cells are a separate population from the serotonin-producing enterochromaffin cells.J. Histochem. Cytochem. 1984; 32: 1066-1074
- Phenotypic characterization of taste cells of the mouse small intestine.Am. J. Physiol. Gastrointest. Liver Physiol. 2007; 292: G1420-G1428
- Serotonin secretion by human carcinoid BON cells.Ann. N. Y. Acad. Sci. 2004; 1014: 179-188
- Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007; 293: R64-R69
- Evidence for a 5-HT3 receptor involvement in the facilitation of peristalsis on mucosal application of 5-HT in the guinea pig isolated ileum.Br. J. Pharmacol. 1997; 122: 1174-1178
- The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat.Br. J. Pharmacol. 2000; 130: 1031-1036
- Electrochemical detection of neurotransmitters in the gut wall.Neurogastroenterol. Motil. 2008; 20: 1185-1188
- Synthesis, storage, release, and metabolism of 5-hydroxytryptamine in peripheral tissues.in: Fozard J.R. The Peripheral Actions of 5-HT. Oxford Medical Publications, Oxford1989: 1-25
- Serotonin content and argentaffin and Paneth cell changes in ulcerative colitis.Gastroenterology. 1962; 43: 24-31
- Ultrastructure of enterochromaffin cells and associated neural and vascular elements in the mouse duodenum.Cell Tissue Res. 1985; 241: 557-563
- Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract.J. Neurosci. 1996; 16: 2352-2364
- Synthesis of serotonin by a second tryptophan hydroxylase isoform.Science. 2003; 299: 76
- CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection.Gut. 2007; 56: 949-957
- p-Chlorophenylalanine depletion of gastrointestinal 5-hydroxytryptamine.Biochem. Pharmacol. 1970; 19: 2169-2172
- Establishment of conditionally immortalized epithelial cell lines from the intestinal tissue of adult normal and transgenic mice.Am. J. Physiol. Gastrointest. Liver Physiol. 2009; 296: G455-G460
- Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.Cell. 2008; 135: 825-837
- Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women.Gut. 2004; 53: 1452-1458
- Expression of taste receptor molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes.Gut. 2009; 58: 337-346
- Immunohistochemical localization of tryptophan hydroxylase in the human and rat gastrointestinal tracts.J. Comp. Neurol. 1999; 411: 654-665
Article info
Publication history
Accepted:
August 10,
2009
Received in revised form:
July 19,
2009
Received:
April 6,
2009
Identification
Copyright
© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
