Enterochromaffin cell

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Enterochromaffin cell
Serotonin-2D-skeletal.svg
Serotonin
Details
Identifiers
Latin endocrinocytus EC
MeSH D004759
TH H3.04.02.0.00029
FMA 62934
Anatomical terms of microanatomy

Enterochromaffin (EC) cells (also known as Kulchitsky cells) are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal regulation, particularly intestinal motility and secretion. [1] They were discovered by Nikolai Kulchitsky. [2]

Contents

EC cells modulate neuron signalling in the enteric nervous system (ENS) via the secretion of the neurotransmitter serotonin and other peptides. As enteric afferent and efferent nerves do not protrude into the intestinal lumen, EC cells act as a form of sensory transduction. [1] However, recent research has shown the direct vagal connection to a specialized entero-endocrine cell, the neuropod cell. ECs known as neuropod cells rapidly relay signals from gut to brain via a direct communication with vagal and primary sensory neurons. [3] Serotonin in the ENS acts in synergy with other digestive hormones to regulate sensory and motor gastrointestinal reflexes. EC cells respond to both chemical and neurological stimuli. They are also reactive to mechanosensation, which is the case in the peristaltic reflex of the gut, and can be stimulated by a bolus moving through the bowel. Upon activation, EC cells release serotonin to act upon serotonin receptors on ENS neurons. Dependent on concentration, serotonin can then modulate peristaltic contraction and secretion through activation of smooth muscle and glands, respectively. [4]

Pulmonary neuroendocrine cells in the respiratory tract are known as bronchial Kulchitsky cells. [5]

Structure

EC cells are small polygonal cells located in the crypts between intestinal villi. They are discriminated from other cells of the gastrointestinal epithelial crypts by the presence of basally located granulations that contain serotonin and other peptides. Ultrastructurally, these granules are reported to vary in size and shape and are considered pleomorphic. [6]

Most EC cells communicate with the lumen of intestinal crypts through apical microvilli (protrusions) and are referred to as “open”. A proportion of EC cells do not protrude into the crypt lumen and are subsequently referred to as ‘closed’. [7] EC cells typically extend down to the basal lamina with cytoplasmic extensions known to pass through the connective tissue and neighbouring glands. Tissue beneath EC cells typically contains abundant fenestrated capillaries, lymph vessels and small unmyelinated nerve fibres. Secreted serotonin can either be taken up into residing vessels (transported in the blood by platelets) or act on nerve synaptic terminals. [6]

Distribution

EC cells are found aggregated in specific locations throughout the gastrointestinal tract, predominantly in the small intestine, colon and appendix. [8] The proportion of high-density cell populations varies between species attributed to differences in dietary requirements and physiological characteristics. [9]

Enterochromaffin-like cells

Enterochromaffin-like cells (ECL cells) are a population of cells that are found in the gastric glands of the stomach luminal epithelium and secrete histamine. In response to gastrin released by neighbouring G-cells, secreted histamine from ECL cells acts on parietal cells to stimulate the release of gastric acid. The presence of ECL cells is critical in regulation of endocrine-induced gastric acid secretion. [10] ECL cells histologically appear similar to EC cells and are hence named as such. They are however a different cell type and do not possess any serotonin synthesizing mechanisms.[ citation needed ]

Development

In developing chick embryos, EC cells have been found in biopsies of developing GIT tissue before the migration of neural crest cells. Whilst EC cells have neuroendocrine properties and are similar chemically and histologically to cells of the adrenal medulla they are not derivatives of the neural crest and do not share a similar cell progenitor. [11] EC cells are believed to be derived from endodermal origins and are descended from the stem cells that form other epithelial cell types of the gastrointestinal lumen. [12]

Function

The primary function of EC cells is to synthesise and secrete serotonin for modulation of gastrointestinal neurons. Serotonin, also named 5-hydroxytryptamine (5HT), can be classified as a hormone, neurotransmitter and a mitogen. It is primarily known for its role in the central nervous system but plays an important role in the periphery, with the largest endogenous pool of serotonin residing in the gut (90% of endogenous store). In the ENS, serotonin is an essential modulator of sensory transduction and mucus secretion. Release of serotonin from EC cells can be triggered by a multitude of stimuli, particularly luminal distension, parasympathetic innervation or changes in osmotic concentrations in intestinal contents. [13]

Serotonin synthesis

The synthesis of 5-HT, in EC cells, is catalyzed by the enzyme tryptophan hydroxylase 1 (TpH1) from the amino acid L-tryptophan. The reaction proceeds in two stages with an initial rate limiting step involving the conversion of L-tryptophan to 5-hydroxytryptophan (5-HTP). Following conversion to 5-HTP, the non-rate limiting L-amino acid decarboxylase converts 5-HTP to 5-HT by decarboxylation. Following synthesis, 5-HT is then stored in vesicles by vesicular monoamine transporter 1 close to the basal margin of the cell for eventual secretion. [1]

Release of the vesicles occurs after chemical, neurological or mechanical stimulation of the EC cells and is predominantly calcium dependent, suggesting excretion via exocytosis. The combined effect of increased calcium flux and a liberation of stored calcium within the cell changes the cell potential triggering release of the 5-HT vesicles. [14] The vesicles pass from the basal margin into the surrounding lamina propria for interaction with nearby nerve synapses, lymph and blood vessels.

The serotonin synthesised by EC cells is predominately exocytosed from the basal border, but is also known to be apically secreted into the lumen of the gut and can be present in faecal samples. Secreted 5-HT acts on different receptor subtypes found localised in cells in the gastrointestinal epithelium, smooth muscle and connective tissue with responsiveness dependent on the concentration of the secreted hormone. [6]

The primary effect of serotonin involves the increase in peristaltic contraction through its effects on both ENS neurons and smooth muscle. 5-HT also activates a neural secretory response, whereby binding at 5-HT1P receptors on myenteric neurons triggers a signalling cascade in the submucosal plexus. This results in the release of acetylcholine to initiate secretion from the gut mucosa via release of chloride ions. [15]

Clinical significance

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a diverse condition associated with chronic bowel discomfort and abdominal pain that ranges in severity between patients. Abnormal concentrations of serotonin have been associated with IBS, predominantly increased concentrations intensifying gastrointestinal motility and mucosal secretions from the gut mucosa. Severe IBS often manifests as either chronic constipation or chronic diarrhoea, and abnormal EC cell populations have been correlated with both conditions. In patients suffering post-infectious IBS, rectal biopsies have shown a dramatic increase in populations of EC cells associated with diarrhoeal symptoms. [16]

Likewise, reduced populations of EC cells in patients suffering chronic constipation have been observed, indicating a lack of 5-HT, and therefore decreased GI motility and secretion. Ongoing research indicates that abnormal EC cell populations, and therefore 5-HT signalling, may significantly contribute to gastrointestinal dysfunction. Treatment using 5-HT-receptor agonists for patients with functional constipation have shown some effectiveness in achieving normal GI functionality. [17]

Carcinoid syndrome

Carcinoid syndrome is a rare condition characterized by an abnormal increase in circulating biologically active hormones, largely serotonin, with early symptoms involving diarrhea, abdominal cramping and episodic flushing. [7] Excess circulating serotonin is usually manufactured by EC-cell-originated carcinoid tumors in the small bowel or appendix. Tumors are slow growing, but can metastasise to the liver if aggressive. They can also be present at other sites, particularly the lung and stomach. [18]

History

The name ‘enterochromaffin’ comes from the Greek word “enteron” (ἔντερον), in relation to intestines, and “chromaffin” as a grouping of the words chromium and affinity, as they can be visualised by staining with chromium salts. Similarly named, chromaffin cells (of the adrenal medulla) share this characteristic and are histologically similar to EC cells. Their embryological origins, however, are quite different, nor do they possess similar functions.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Gastrointestinal tract</span> Organ system within humans and other animals

The gastrointestinal tract is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and other animals, including the esophagus, stomach, and intestines. Food taken in through the mouth is digested to extract nutrients and absorb energy, and the waste expelled at the anus as faeces. Gastrointestinal is an adjective meaning of or pertaining to the stomach and intestines.

<span class="mw-page-title-main">Enteric nervous system</span> Vital system controlling the gastrointestinal tract

The enteric nervous system (ENS) or is one of the three divisions of the autonomic nervous system (ANS), the others being the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). It consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. It is capable of acting independently of the SNS and PSNS, although it may be influenced by them. The ENS is nicknamed the "second brain". It is derived from neural crest cells.

<span class="mw-page-title-main">Gastric acid</span> Digestive fluid formed in the stomach

Gastric acid or stomach acid is the acidic component – hydrochloric acid of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. With a pH of between one and three, gastric acid plays a key role in the digestion of proteins by activating digestive enzymes, which together break down the long chains of amino acids of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce mucus – a viscous barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to neutralize gastric acid passing into the digestive tract.

<span class="mw-page-title-main">Myenteric plexus</span> Part of the enteric nervous system

The myenteric plexus provides motor innervation to both layers of the muscular layer of the gut, having both parasympathetic and sympathetic input, whereas the submucous plexus provides secretomotor innervation to the mucosa nearest the lumen of the gut.

Functional gastrointestinal disorders (FGID), also known as disorders of gut–brain interaction, include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and motility disturbances.

A neurohormone is any hormone produced and released by neuroendocrine cells into the blood. By definition of being hormones, they are secreted into the circulation for systemic effect, but they can also have a role of neurotransmitter or other roles such as autocrine (self) or paracrine (local) messenger.

<span class="mw-page-title-main">Enterochromaffin-like cell</span>

Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell found in the gastric glands of the gastric mucosa beneath the epithelium, in particular in the vicinity of parietal cells, that aid in the production of gastric acid via the release of histamine. They are also considered a type of enteroendocrine cell.

<span class="mw-page-title-main">Goblet cell</span> Epithelial cells that secrete mucins

Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secretions, when under stress. The term goblet refers to the cell's goblet-like shape. The apical portion is shaped like a cup, as it is distended by abundant mucus laden granules; its basal portion lacks these granules and is shaped like a stem.

<span class="mw-page-title-main">Carcinoid</span> Slow-growing type of neuroendocrine tumor

A carcinoid is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut are associated with carcinoid syndrome.

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors. The syndrome is caused by neuroendocrine tumors most often found in the gut releasing biologically active substances into the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction.

<span class="mw-page-title-main">Gastrinoma</span> Medical condition

Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.

<span class="mw-page-title-main">Gastric glands</span> Glands in lining of the human stomach

Gastric glands are glands in the lining of the stomach that play an essential role in the process of digestion. Their secretions make up the digestive gastric juice. The gastric glands open into gastric pits in the mucosa. The gastric mucosa is covered in surface mucous cells that produce the mucus necessary to protect the stomach's epithelial lining from gastric acid secreted by parietal cells in the glands, and from pepsin, a secreted digestive enzyme. Surface mucous cells follow the indentations and partly line the gastric pits. Other mucus secreting cells are found in the necks of the glands. These are mucous neck cells that produce a different kind of mucus.

<span class="mw-page-title-main">Vesicular monoamine transporter 1</span> Protein-coding gene in the species Homo sapiens

Vesicular monoamine transporter 1 (VMAT1) also known as chromaffin granule amine transporter (CGAT) or solute carrier family 18 member 1 (SLC18A1) is a protein that in humans is encoded by the SLC18A1 gene. VMAT1 is an integral membrane protein, which is embedded in synaptic vesicles and serves to transfer monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin, between the cytosol and synaptic vesicles. SLC18A1 is an isoform of the vesicular monoamine transporter.

<span class="mw-page-title-main">Neuroendocrine tumor</span> Tumors of the endocrine and nervous systems

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body.

<span class="mw-page-title-main">Enteroendocrine cell</span> Cell that produces gastrointestinal hormones

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and excrete waste products. The GI tract is composed of the alimentary canal, that runs from the mouth to the anus, as well as the associated glands, chemicals, hormones, and enzymes that assist in digestion. The major processes that occur in the GI tract are: motility, secretion, regulation, digestion and circulation. The proper function and coordination of these processes are vital for maintaining good health by providing for the effective digestion and uptake of nutrients.

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<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

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<span class="mw-page-title-main">Intestinal mucosal barrier</span>

The intestinal mucosal barrier, also referred to as intestinal barrier, refers to the property of the intestinal mucosa that ensures adequate containment of undesirable luminal contents within the intestine while preserving the ability to absorb nutrients. The separation it provides between the body and the gut prevents the uncontrolled translocation of luminal contents into the body proper. Its role in protecting the mucosal tissues and circulatory system from exposure to pro-inflammatory molecules, such as microorganisms, toxins, and antigens is vital for the maintenance of health and well-being. Intestinal mucosal barrier dysfunction has been implicated in numerous health conditions such as: food allergies, microbial infections, irritable bowel syndrome, inflammatory bowel disease, celiac disease, metabolic syndrome, non-alcoholic fatty liver disease, diabetes, and septic shock.

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References

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  2. ↑ Drozdov I, Modlin IM, Kidd M, Goloubinov VV (February 2009). "Nikolai Konstantinovich Kulchitsky (1856-1925)". Journal of Medical Biography. 17 (1): 47–54. doi:10.1258/jmb.2008.008038. PMID   19190200. S2CID   25289790.
  3. ↑ Barton JR, Londregan AK, Alexander TD, Entezari AA, Covarrubias M, Waldman SA (2023-11-07). "Enteroendocrine cell regulation of the gut-brain axis". Frontiers in Neuroscience. 17: 1272955. doi: 10.3389/fnins.2023.1272955 . PMC   10662325 . PMID   38027512.
  4. ↑ Mawe GM, Hoffman JM (August 2013). "Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets". Nature Reviews. Gastroenterology & Hepatology. 10 (8): 473–486. doi:10.1038/nrgastro.2013.105. PMC   4048923 . PMID   23797870.
  5. ↑ Becker KL, Silva OL (July 1981). "Hypothesis: the bronchial Kulchitsky (K) cell as a source of humoral biologic activity". Medical Hypotheses. 7 (7): 943–949. doi:10.1016/0306-9877(81)90049-9. PMID   6270516.
  6. 1 2 3 Wade PR, Westfall JA (1985). "Ultrastructure of enterochromaffin cells and associated neural and vascular elements in the mouse duodenum". Cell and Tissue Research. 241 (3): 557–563. doi:10.1007/BF00214576. PMID   4028141. S2CID   33773512.
  7. 1 2 Gustafsson BI (2005). The Serotonin Producing Enterochromaffin Cell, and Effects of Hyperserotoninemia on Heart and Bone (PhD Thesis). Det medisinske fakultet. hdl:11250/263149. ISBN   9788247173121.[ page needed ]
  8. ↑ Graeme-Cook F (2009). "Neuroendocrine Tumors of the GI Tract and Appendix". In Odze RD, Goldblum JR (eds.). Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. pp. 653–80. doi:10.1016/B978-141604059-0.50028-X. ISBN   978-1-4160-4059-0.
  9. ↑ Al-Tikriti MS, Khamas W, Chebolu S, Darmani NA (2012). "Distribution of Serotonin-Immunoreactive Enterochromaffin Cells in the Gastrointestinal Tract of the Least Shrew" (PDF). Int. J. Morphol. 30 (3): 916–23. doi: 10.4067/s0717-95022012000300025 .
  10. ↑ Prinz C, Zanner R, Gerhard M, Mahr S, Neumayer N, Höhne-Zell B, et al. (November 1999). "The mechanism of histamine secretion from gastric enterochromaffin-like cells". The American Journal of Physiology. 277 (5): C845–C855. doi:10.1152/ajpcell.1999.277.5.C845. PMID   10564076.
  11. ↑ Andrew A (June 1974). "Further evidence that enterochromaffin cells are not derived from the neural crest". Journal of Embryology and Experimental Morphology. 31 (3): 589–598. PMID   4448939.
  12. ↑ Thompson M, Fleming KA, Evans DJ, Fundele R, Surani MA, Wright NA (October 1990). "Gastric endocrine cells share a clonal origin with other gut cell lineages". Development. 110 (2): 477–481. doi: 10.1242/dev.110.2.477 . PMID   2133551.
  13. ↑ Manocha M, Khan WI (April 2012). "Serotonin and GI Disorders: An Update on Clinical and Experimental Studies". Clinical and Translational Gastroenterology. 3 (4): e13. doi:10.1038/ctg.2012.8. PMC   3365677 . PMID   23238212.
  14. ↑ Racké K, Reimann A, Schwörer H, Kilbinger H (1995). "Regulation of 5-HT release from enterochromaffin cells". Behavioural Brain Research. 73 (1–2): 83–87. doi:10.1016/0166-4328(96)00075-7. PMID   8788482. S2CID   3948073.
  15. ↑ Sidhu M, Cooke HJ (September 1995). "Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion". The American Journal of Physiology. 269 (3 Pt 1): G346–G351. doi:10.1152/ajpgi.1995.269.3.G346. PMID   7573444.
  16. ↑ Lee KJ, Kim YB, Kim JH, Kwon HC, Kim DK, Cho SW (November 2008). "The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors". Journal of Gastroenterology and Hepatology. 23 (11): 1689–1694. doi:10.1111/j.1440-1746.2008.05574.x. PMID   19120860. S2CID   205463559.
  17. ↑ El-Salhy M, Norrgård O, Spinnell S (October 1999). "Abnormal colonic endocrine cells in patients with chronic idiopathic slow-transit constipation". Scandinavian Journal of Gastroenterology. 34 (10): 1007–1011. doi:10.1080/003655299750025110. PMID   10563671.
  18. ↑ Berge T, Linell F (July 1976). "Carcinoid tumours. Frequency in a defined population during a 12-year period". Acta Pathologica et Microbiologica Scandinavica, Section A. 84 (4): 322–330. doi:10.1111/j.1699-0463.1976.tb00122.x. PMID   961424.
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