Chromaffin cell

Last updated
Medullary chromaffin cell
Gray1185.png
Adrenal gland. (Medulla labeled at bottom right.)
Details
LocationMedulla adrenal gland
Identifiers
Latin endocrinocytus medullaris
MeSH D019439
TH H3.08.02.6.00015
FMA 69263
Anatomical terms of microanatomy

Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. 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. [1] 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 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 catecholamines: ~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.

Contents

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): [2]

1) 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. [3]

2) 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. [4] 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. [2]

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. [5] [6]

Function

Adrenaline (Epinephrine) Adrenaline.svg
Adrenaline (Epinephrine)
Noradrenaline (Norepinephrine) Norepinephrine structure.png
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 endorphins (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. [7] 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. [8]

Catecholamine biosynthesis Catecholamine biosynthesis.png
Catecholamine biosynthesis

Clinical significance

Neoplasms arising from these cells are pheochromocytomas (also called chromaffin or sympathetic paragangliomas, in contrast to non-chromaffin or parasympathetic paragangliomas 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 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 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. [9] 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. [10]

History

The word "chromaffin" comes from a portmanteau of chromium and affinity. They are named as such because they can be visualised by staining 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 cells near sympathetic ganglia.

See also

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal 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 cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

<span class="mw-page-title-main">Autonomic nervous system</span> Division of the nervous system supplying internal organs, smooth muscle and glands

The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the nervous system that operates internal organs, smooth muscle and glands. The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions, such as the heart rate, its force of contraction, digestion, respiratory rate, pupillary response, urination, and sexual arousal. This system is the primary mechanism in control of the fight-or-flight response.

<span class="mw-page-title-main">Sympathetic nervous system</span> Part of the autonomic nervous system which stimulates fight-or-flight responses

The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

<span class="mw-page-title-main">Pheochromocytoma</span> Type of neuroendocrine tumor

Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred to as a paraganglioma. These neuroendocrine tumors typically release massive amounts of catecholamines which result in the most common symptoms, including hypertension, tachycardia, and sweating. Rarely, some tumors may secrete little to no catecholamines, making diagnosis difficult. While tumors of the head and neck are parasympathetic, their sympathetic counterparts are predominantly located in the abdomen and pelvis, particularly concentrated at the organ of Zuckerkandl.

<span class="mw-page-title-main">Adrenal medulla</span> Central part of the adrenal gland

The adrenal medulla is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine, in response to stimulation by sympathetic preganglionic neurons.

<span class="mw-page-title-main">Muscarinic acetylcholine receptor</span> Acetylcholine receptors named for their selective binding of muscarine

Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system.

<span class="mw-page-title-main">Paraganglioma</span> Rare neuroendocrine tumour

A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites. When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They are rare tumors, with an overall estimated incidence of 1 in 300,000. There is no test that determines benign from malignant tumors; long-term follow-up is therefore recommended for all individuals with paraganglioma.

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">Organ of Zuckerkandl</span>

The organ of Zuckerkandl is a chromaffin body derived from the neural crest located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery. It can be the source of a paraganglioma.

<span class="mw-page-title-main">Postganglionic nerve fibers</span> Fibers from the ganglion to the effector organ

In the autonomic nervous system, nerve fibers from the ganglion to the effector organ are called postganglionic nerve fibers.

<span class="mw-page-title-main">Vanillylmandelic acid</span> Chemical compound

Vanillylmandelic acid (VMA) is a chemical intermediate in the synthesis of artificial vanilla flavorings and is an end-stage metabolite of the catecholamines. It is produced via intermediary metabolites.

<span class="mw-page-title-main">Paraganglion</span>

A paraganglion is a group of non-neuronal cells derived of the neural crest. They are named for being generally in close proximity to sympathetic ganglia. They are essentially of two types: (1) chromaffin or sympathetic paraganglia made of chromaffin cells and (2) nonchromaffin or parasympathetic paraganglia made of glomus cells. They are neuroendocrine cells, the former with primary endocrine functions and the latter with primary chemoreceptor functions.

<span class="mw-page-title-main">Phenylethanolamine N-methyltransferase</span> Mammalian protein found in Homo sapiens

Phenylethanolamine N-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline). It is also expressed in small groups of neurons in the human brain and in selected populations of cardiomyocytes.

<span class="mw-page-title-main">Norepinephrine</span> Catecholamine hormone and neurotransmitter

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" is more commonly used in the United Kingdom, whereas "norepinephrine" is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.

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

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.

<span class="mw-page-title-main">Iobenguane</span> Chemical compound

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in neuroendocrine chemotherapy treatments.

<span class="mw-page-title-main">Adrenaline</span> Hormone and medication

Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions. It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant Scoparia dulcis found in Northern Vietnam.

<span class="mw-page-title-main">Sympathoadrenal system</span>

The sympathoadrenal system is a physiological connection between the sympathetic nervous system and the adrenal medulla and is crucial in an organism's physiological response to outside stimuli. When the body receives sensory information, the sympathetic nervous system sends a signal to preganglionic nerve fibers, which activate the adrenal medulla through acetylcholine. Once activated, norepinephrine and epinephrine are released directly into the blood by adrenomedullary cells where they act as the bodily mechanism for "fight-or-flight" responses. Because of this, the sympathoadrenal system plays a large role in maintaining glucose levels, sodium levels, blood pressure, and various other metabolic pathways that couple with bodily responses to the environment. During numerous diseased states, such as hypoglycemia or even stress, the body's metabolic processes are skewed. The sympathoadrenal system works to return the body to homeostasis through the activation or inactivation of the adrenal gland. However, more severe disorders of the sympathoadrenal system such as pheochromocytoma can affect the body's ability to maintain a homeostatic state. In these cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla.

<span class="mw-page-title-main">History of catecholamine research</span>

The catecholamines are a group of neurotransmitters composed of the endogenous substances dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine), as well as numerous artificially synthesized compounds such as isoprenaline - an anti-bradycardiac medication. Their investigation constitutes a major chapter in the history of physiology, biochemistry, and pharmacology. Adrenaline was the first hormone extracted from an endocrine gland and obtained in pure form, before the word hormone was coined. Adrenaline was also the first hormone whose structure and biosynthesis was discovered. Second to acetylcholine, adrenaline and noradrenaline were some of the first neurotransmitters discovered, and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor gene was the first G protein-coupled receptor to be cloned.

References

  1. ↑ Schober, Andreas; Parlato, Rosanna; Huber, Katrin; Kinscherf, Ralf; Hartleben, Björn; Huber, Tobias B; Schütz, Günther; Unsicker, Klaus (2013). "Cell Loss and Autophagy in the Extra-Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling". Journal of Neuroendocrinology. 25 (1): 34–47. doi:10.1111/j.1365-2826.2012.02367.x. ISSN   0953-8194. PMC   3564403 . PMID   23078542.
  2. 1 2 "Chapter 179. The Paraganglionic System: The Paraganglia - Review of Medical Embryology Book - LifeMap Discovery". discovery.lifemapsc.com. Archived from the original on 2016-12-20. Retrieved 2017-06-03.
  3. ↑ "Chapter 164. The Autonomic Nervous System: The Sympathetic System - Review of Medical Embryology Book - LifeMap Discovery". discovery.lifemapsc.com. Archived from the original on 2017-05-05. Retrieved 2017-06-03.
  4. ↑ Schober, Andreas; Parlato, Rosanna; Huber, Katrin; Kinscherf, Ralf; Hartleben, Björn; Huber, Tobias B.; Schütz, Günther; Unsicker, Klaus (1 January 2013). "Cell Loss and Autophagy in the Extra-Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling". Journal of Neuroendocrinology. 25 (1): 34–47. doi:10.1111/j.1365-2826.2012.02367.x. PMC   3564403 . PMID   23078542.
  5. ↑ Perry, SF; Capaldo, A (Nov 16, 2011). "The autonomic nervous system and chromaffin tissue: neuroendocrine regulation of catecholamine secretion in non-mammalian vertebrates". Autonomic Neuroscience: Basic and Clinical. 165 (1): 54–66. doi:10.1016/j.autneu.2010.04.006. PMID   20547474. S2CID   42402600.
  6. ↑ Pohorecky, LA; Wurtman, RJ (Mar 1971). "Adrenocortical control of epinephrine synthesis" (PDF). Pharmacological Reviews. 23 (1): 1–35. PMID   4941407. Archived from the original (PDF) on 2016-03-05. Retrieved 2013-03-01.
  7. ↑ Szewczyk, A; Lobanov, NA; Kicińska, A; Wójcik, G; Nałecz, MJ (2001). "ATP-sensitive K+ transport in adrenal chromaffin granules" (PDF). Acta Neurobiologiae Experimentalis. 61 (1): 1–12. PMID   11315316. Archived from the original (PDF) on 2017-08-09. Retrieved 2013-02-25.
  8. ↑ Young; Lowe; Stevens; Heath, eds. (2006). Wheater's Functional Histology (5th ed.). Edinburgh: Churchill Livingstone. ISBN   978-0-443-06850-8.
  9. ↑ Jafferjee, Malika; Reyes Valero, Thairy; Marrero, Christine; McCrink, Katie A.; Brill, Ava; Lymperopoulos, Anastasios (2016-03-01). "GRK2 Up-Regulation Creates a Positive Feedback Loop for Catecholamine Production in Chromaffin Cells". Molecular Endocrinology. 30 (3): 372–381. doi:10.1210/me.2015-1305. ISSN   0888-8809. PMC   5414648 . PMID   26849467.
  10. ↑ Lymperopoulos, Anastasios; Rengo, Giuseppe; Gao, Erhe; Ebert, Steven N.; Dorn, Gerald W.; Koch, Walter J. (2010-05-21). "Reduction of Sympathetic Activity via Adrenal-targeted GRK2 Gene Deletion Attenuates Heart Failure Progression and Improves Cardiac Function after Myocardial Infarction". Journal of Biological Chemistry. 285 (21): 16378–16386. doi: 10.1074/jbc.M109.077859 . ISSN   0021-9258. PMC   2871505 . PMID   20351116.

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