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Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...
s in
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
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. They are in close proximity to pre-synaptic sympathetic ganglia of the
sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...
, with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the
splanchnic nerve The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system ( visceral efferent fibers) as well as sensory fibers from the organs ( viscera ...
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 A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...
s: ~80% of
adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...
(
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...
) and ~20% of
noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" (from ...
(
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
) into
systemic circulation In vertebrates, the circulatory system is a organ system, system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of ...
for systemic effects on multiple organs (similarly to secretory neurones of the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
), and can also send
paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
signals. Hence they are called neuroendocrine cells.


Embryonic origin and structure

There are two types of cells that originate from the
neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...
and are related to the sympathetic nervous system (originate from a cell called sympathogonia): #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. #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. Tumors arising from these cell are called paragangliomas or 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. Chromaffin cells also settle near the
vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
and
carotid arteries In anatomy, the left and right common carotid arteries (carotids) () are arteries that supply the head and neck with oxygenated blood; they divide in the neck to form the external and internal carotid arteries. Structure The common carotid ...
. In lower concentrations, extra-adrenal chromaffin cells also reside in the
bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...
wall,
prostate The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...
, and behind the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
. 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 The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...
or
paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
signals for secretion.


Function

Chromaffin cells of the adrenal medulla are innervated by the
splanchnic nerve The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system ( visceral efferent fibers) as well as sensory fibers from the organs ( viscera ...
and secrete adrenaline (
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...
), noradrenaline (
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
), some
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
,
enkephalin An enkephalin is a pentapeptide involved in regulating nociception (pain sensation) in the body. The enkephalins are termed endogenous ligands, as they are internally derived (and therefore endogenous) and bind as ligands to the body's opioid ...
and enkephalin-containing peptides, and a few other hormones into the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
stream. The secreted adrenaline and noradrenaline play an important role in the sympathetic nervous system response, commonly called the
fight-or-flight response The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first describ ...
. The enkephalins and enkephalin-containing peptides are related to, but distinct from endogenous peptides named
endorphin Endorphins (contracted from endogenous morphine) are peptides produced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in the pituitary gland of the brain. Endorphins are endogeno ...
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. 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.


Clinical significance

Neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s arising from these cells are
pheochromocytoma Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...
s (also called chromaffin or sympathetic paragangliomas, in contrast to non-chromaffin or parasympathetic
paraganglioma A paraganglioma is a rare neuroendocrine tumour, neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a p ...
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 Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
, the body increases sympathetic activity to the adrenal medulla as the compensatory mechanism to increase heart rate and
cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...
. 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 α2 adrenergic receptors on their cell membrane. This desensitization and downregulation of α2 adrenergic receptors is caused by the upregulation of the enzyme Adrenal G protein coupled receptor kinase 2 ( GRK2) which effectively eliminates the normal autocrine-type
negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...
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. This upregulation of GRK2 is also accompanied by upregulation and increased production of the enzyme
tyrosine hydroxylase Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and ...
, which catalyzes the rate limiting step of catecholamine synthesis.


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 A stain is a discoloration that can be clearly distinguished from the surface, material, or medium it is found upon. They are caused by the chemical or physical interaction of two dissimilar materials. Accidental staining may make materials app ...
ing with
chromium Chromium is a chemical element; it has Symbol (chemistry), symbol Cr and atomic number 24. It is the first element in Group 6 element, group 6. It is a steely-grey, Luster (mineralogy), lustrous, hard, and brittle transition metal. Chromium ...
salts. Chromium salts oxidise and polymerise
catecholamines A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. ...
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 cells near sympathetic ganglia.


See also

*
List of distinct cell types in the adult human body The list of human cell types provides an enumeration and description of the various specialized cells found within the human body, highlighting their distinct functions, characteristics, and contributions to overall physiological processes. Cell ...
*
List of human cell types derived from the germ layers This is a list of Cell (biology), cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte (human), Trichocyte * Keratinocyte Anterior pi ...


References


External links

* - "Endocrine System: adrenal gland, reticularis and medulla"
Secretion Control in Adrenal Chromaffin Cells

UC-San Diego Chromaffin Cell and Hypertension Research



Rat Chromaffin cells primary cultures: Standardization and quality assessment for single-cell assays (a protocol)

Chromaffin Cell Stain (Giemsa Staining Method)
{{Authority control Endocrine system anatomy Neuroendocrine cells Human cells Adrenal gland