Editing Chromaffin cell

{{short description|Neuroendocrine cells found in adrenal medulla in mammals}}
{{Infobox cell
| Name        = Medullary chromaffin cell
| Latin       = endocrinocytus medullaris
| Image       = Gray1185.png
| Caption     = Adrenal gland. (Medulla labeled at bottom right.)
| Image2      =
| Caption2    =
| Precursor   =
| System      =
| Location = Medulla [[adrenal gland]]
}}
'''Chromaffin cells''', also called '''pheochromocytes''' (or '''phaeochromocytes'''), are [[neuroendocrine cell]]s found mostly in the [[adrenal medulla|medulla]] of the [[adrenal gland]]s  in [[mammal]]s. These cells serve a variety of functions such as serving as a response to stress, monitoring carbon dioxide and oxygen concentrations in the body, maintenance of respiration and the regulation of blood pressure.<ref>{{Cite journal|last1=Schober|first1=Andreas|last2=Parlato|first2=Rosanna|last3=Huber|first3=Katrin|last4=Kinscherf|first4=Ralf|last5=Hartleben|first5=Björn|last6=Huber|first6=Tobias B|last7=Schütz|first7=Günther|last8=Unsicker|first8=Klaus|year = 2013|title=Cell Loss and Autophagy in the Extra-Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling|journal=Journal of Neuroendocrinology|volume=25|issue=1|pages=34–47|doi=10.1111/j.1365-2826.2012.02367.x|issn=0953-8194|pmc=3564403|pmid=23078542}}</ref>  They are in close proximity to pre-synaptic [[sympathetic ganglia]] of the [[sympathetic nervous system]], with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the [[Splanchnic nerves|splanchnic nerve]] of the sympathetic nervous system releases acetylcholine, which then binds to nicotinic acetylcholine receptors on the adrenal medulla. This causes the release of catecholamines. The chromaffin cells release [[catecholamine]]s: ~80% of [[adrenaline]] ([[epinephrine]]) and ~20%  of [[noradrenaline]] ([[norepinephrine]]) into [[systemic circulation]] for systemic effects on multiple organs (similarly to secretory neurones of the [[hypothalamus]]), and can also send [[paracrine]] signals. Hence they are called neuroendocrine cells.

==Embryonic origin and structure==
There are two types of cells that originate from the [[neural crest]] and are related to the sympathetic nervous system (originate from a cell called sympathogonia):<ref name=":0">{{Cite web|url=https://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-179-the-paraganglionic-system-the-paraganglia|title=Chapter 179. The Paraganglionic System: The Paraganglia - Review of Medical Embryology Book - LifeMap Discovery|website=discovery.lifemapsc.com|access-date=2017-06-03|archive-url=https://web.archive.org/web/20161220182718/http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-179-the-paraganglionic-system-the-paraganglia|archive-date=2016-12-20|url-status=dead}}</ref>
#'''Neuroblasts''': These cells migrate, during the fourth to the fifth week of fetal development in humans, on both sides of the spinal cord toward the region just behind the dorsal aorta forming the two chains of sympathetic ganglia (Sympathetic chain). From these ganglia, the post synaptic sympathetic fibers will arise and extend toward their target organ. Some of these cells will migrate to the adrenal medulla to form sympathetic ganglia cells within the adrenal medulla (without postsynaptic sympathetic fibers). A tumor arising from these cells is called neuroblastoma.<ref>{{Cite web|url=https://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-164-the-autonomic-nervous-system-the-sympathetic-system|title=Chapter 164. The Autonomic Nervous System: The Sympathetic System - Review of Medical Embryology Book - LifeMap Discovery|website=discovery.lifemapsc.com|access-date=2017-06-03|archive-url=https://web.archive.org/web/20170505102854/http://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-164-the-autonomic-nervous-system-the-sympathetic-system|archive-date=2017-05-05|url-status=dead}}</ref>
#'''Chromaffin cells''' (or pheochromocytes): These cells will migrate to the area adjacent to the sympathetic ganglia (hence the name paraganglia) and to the adrenal medulla where they will be the most abundant type of cells. The largest extra-adrenal cluster of chromaffin cells in mammals is the [[organ of Zuckerkandl]].<ref>{{cite journal|last=Schober|first=Andreas|date=1 January 2013|title=Cell Loss and Autophagy in the Extra-Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling|journal=Journal of Neuroendocrinology|volume=25|issue=1|pages=34–47|doi=10.1111/j.1365-2826.2012.02367.x|pmc=3564403|pmid=23078542|author2=Parlato, Rosanna|author3=Huber, Katrin|author4=Kinscherf, Ralf|author5=Hartleben, Björn|author6=Huber, Tobias B.|author7=Schütz, Günther|author8=Unsicker, Klaus}}</ref> Tumors arising from these cell are called paragangliomas or [[Pheochromocytoma|pheochromocytomas]]. These terms can be used interchangeably but usually paraganglioma refer to a tumor originating from chromaffin cells outside the adrenal gland, which can also be called extra-adrenal pheochromocytoma, whereas pheochromocytoma typically refer to a tumor originating from the chromaffin cells within the adrenal gland.<ref name=":0" />

Chromaffin cells also settle near the [[vagus nerve]] and [[carotid arteries]]. In lower concentrations, extra-adrenal chromaffin cells also reside in the [[bladder]] wall, [[prostate]], and behind the [[liver]].

In non-mammals, chromaffin cells are found in a variety of places, generally not organised as an individual organ, and may be without innervation, relying only on [[endocrine]] or [[paracrine]] signals for secretion.<ref>{{cite journal|last=Perry|first=SF|author2=Capaldo, A|title=The autonomic nervous system and chromaffin tissue: neuroendocrine regulation of catecholamine secretion in non-mammalian vertebrates.|journal=Autonomic Neuroscience: Basic and Clinical|date=Nov 16, 2011|volume=165|issue=1|pages=54–66|pmid=20547474|doi=10.1016/j.autneu.2010.04.006|s2cid=42402600}}</ref><ref>{{cite journal|last=Pohorecky|first=LA|author2=Wurtman, RJ|title=Adrenocortical control of epinephrine synthesis.|journal=Pharmacological Reviews|date=Mar 1971|volume=23|issue=1|pages=1–35|pmid=4941407|url=http://wurtmanlab.mit.edu/static/pdf/151.pdf|access-date=2013-03-01|archive-url=https://web.archive.org/web/20160305054827/http://wurtmanlab.mit.edu/static/pdf/151.pdf|archive-date=2016-03-05|url-status=dead}}</ref>

==Function==
[[File:Epinephrine.svg|thumb|Adrenaline ([[epinephrine]])]]
[[File:Norepinephrine.svg|thumb|Noradrenaline ([[norepinephrine]])]]
Chromaffin cells of the adrenal medulla are innervated by the [[splanchnic nerve]] and secrete adrenaline ([[epinephrine]]), noradrenaline ([[norepinephrine]]), some [[dopamine]], [[enkephalin]] and enkephalin-containing peptides, and a few other hormones into the [[blood]] stream. The secreted adrenaline and noradrenaline play an important role in the sympathetic nervous system response, commonly called the [[fight-or-flight response]]. The enkephalins and enkephalin-containing peptides are related to, but distinct from endogenous peptides named [[endorphin]]s (which are secreted from the pituitary); all of these peptides bind to opioid receptors and produce analgesic (and other) responses. The hormones are secreted from chromaffin granules; this is where the enzyme dopamine β-hydroxylase catalyses the conversion of dopamine to noradrenaline.<ref>{{cite journal|last=Szewczyk|first=A|author2=Lobanov, NA|author3=Kicińska, A|author4=Wójcik, G|author5=Nałecz, MJ|title=ATP-sensitive K+ transport in adrenal chromaffin granules.|journal=Acta Neurobiologiae Experimentalis|year=2001|volume=61|issue=1|pages=1–12|pmid=11315316|url=http://www.ane.pl/pdf/6101.pdf|access-date=2013-02-25|archive-url=https://web.archive.org/web/20170809071040/http://www.ane.pl/pdf/6101.pdf|archive-date=2017-08-09|url-status=dead}}</ref>  Distinct N and E cell forms exist (also Na and A cells in British nomenclature - noradrenaline and adrenaline); the former produce norepinephrine, the latter arise out of N cells through interaction with glucocorticoids, and convert norepinephrine into epinephrine.<ref>{{cite book |title=Wheater's Functional Histology |edition=5th |editor1-last=Young |editor2-last=Lowe |editor3-last=Stevens |editor4-last=Heath |location=Edinburgh |publisher=Churchill Livingstone |isbn=978-0-443-06850-8 |year=2006 }}</ref>

[[File:Catecholamine biosynthesis.png|Catecholamine biosynthesis|center|frameless|700x700px]]

==Clinical significance==
[[Neoplasm]]s arising from these cells are [[pheochromocytoma]]s (also called chromaffin or sympathetic paragangliomas, in contrast to non-chromaffin or parasympathetic [[paraganglioma]]s of glomus cells). Sometimes only neoplasms of adrenal origin are named pheochromocytomas, while others are named extra-adrenal paragangliomas.

=== Heart failure ===
Following [[heart failure]], the body increases sympathetic activity to the adrenal medulla as the compensatory mechanism to increase heart rate and [[cardiac output]]. This increased sympathetic activity leads to chronically increased synthesis and secretion of catecholamines from the adrenal chromaffin cells. This chronic increase of epinephrine and norepinephrine secretion causes desensitization of the chromaffin cells to catecholamines resulting in a decrease in production and presence of α<sub>2</sub> adrenergic receptors on their cell membrane. This desensitization and downregulation of [[Adrenergic receptor|α<sub>2</sub> adrenergic]] receptors is caused by the upregulation of the enzyme Adrenal G protein coupled receptor kinase 2 ([[Beta adrenergic receptor kinase|GRK2]]) which effectively eliminates the normal autocrine-type [[negative feedback]] that normally prevents the cells from over producing the catecholamines and replaces it with a positive feedback loop in which increased secretion further elicits more secretion.<ref>{{Cite journal|last1=Jafferjee|first1=Malika|last2=Reyes Valero|first2=Thairy|last3=Marrero|first3=Christine|last4=McCrink|first4=Katie A.|last5=Brill|first5=Ava|last6=Lymperopoulos|first6=Anastasios|date=2016-03-01|title=GRK2 Up-Regulation Creates a Positive Feedback Loop for Catecholamine Production in Chromaffin Cells|journal=Molecular Endocrinology|volume=30|issue=3|pages=372–381|doi=10.1210/me.2015-1305|issn=0888-8809|pmc=5414648|pmid=26849467}}</ref> This upregulation of GRK2 is also accompanied by upregulation and increased production of the enzyme [[tyrosine hydroxylase]], which catalyzes the rate limiting step of catecholamine synthesis.<ref>{{Cite journal|last1=Lymperopoulos|first1=Anastasios|last2=Rengo|first2=Giuseppe|last3=Gao|first3=Erhe|last4=Ebert|first4=Steven N.|last5=Dorn|first5=Gerald W.|last6=Koch|first6=Walter J.|date=2010-05-21|title=Reduction of Sympathetic Activity via Adrenal-targeted GRK2 Gene Deletion Attenuates Heart Failure Progression and Improves Cardiac Function after Myocardial Infarction|journal=Journal of Biological Chemistry|language=en|volume=285|issue=21|pages=16378–16386|doi=10.1074/jbc.M109.077859|issn=0021-9258|pmc=2871505|pmid=20351116|doi-access=free}}</ref>

==History==
:''See also [[chromophil]].''
The word "chromaffin" comes from a portmanteau of ''chrom''ium and ''affin''ity. They are named as such because they can be visualised by [[stain]]ing with [[chromium]] salts. Chromium salts oxidise and polymerise [[catecholamines]] to form a brown color, most strongly in the cells secreting noradrenaline. Chromaffin cells are also called pheochromocytes.

The [[enterochromaffin cells]] are so named because of their histological similarity to chromaffin cells (they stain yellow when treated with chromium salts), but their function is quite different and they are not derivatives of the neural crest.

[[Paraganglia]] are clusters of either chromaffin cells or [[glomus cell]]s near sympathetic ganglia.

== See also ==
*[[List of distinct cell types in the adult human body]]
*[[List of human cell types derived from the germ layers]]

== References ==
{{Reflist}}

==External links==
* {{BUHistology|14507loa}} - "Endocrine System: adrenal gland, reticularis and medulla"
* [https://web.archive.org/web/20040327103718/http://www.mpibpc.gwdg.de/abteilungen/140/projects/Chromaffin.html Secretion Control in Adrenal Chromaffin Cells]
* [https://web.archive.org/web/20100629072948/http://hypertension.ucsd.edu/ UC-San Diego Chromaffin Cell and Hypertension Research]
* [http://webpages.ull.es/users/isccb12/ChromaffinCell/Primer.html A Primer on Chromaffin Cells]
* [https://web.archive.org/web/20090706190956/http://www.natureprotocols.com/2006/09/29/rat_chromaffin_cells_primary_c.php Rat Chromaffin cells primary cultures: Standardization and quality assessment for single-cell assays (a protocol)]
* [https://pscientifics.com/adrenal-chromaffin-cell-stain-giemsa-staining-method/Adrenal Chromaffin Cell Stain (Giemsa Staining Method)
]
{{Adrenal gland}}
{{Authority control}}

[[Category:Endocrine system anatomy]]
[[Category:Neuroendocrine cells]]
[[Category:Human cells]]
[[Category:Adrenal gland]]