|Medullary chromaffin cell|
Adrenal gland. (Medulla labeled at bottom right.)
Chromaffin cells, also pheochromocytes, are neuroendocrine cells found mostly in the medulla of the adrenal glands (located above the kidneys) in mammals. 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 neurones. 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.
In the mammalian fetal development (the fourth to the fifth week in humans), neuroblast cells migrate from the neural crest to form the sympathetic chain and preaortic ganglia. The cells migrate a second time to the adrenal medulla. Chromaffin cells also settle near the sympathetic ganglia, vagus nerve, paraganglia, and carotid arteries. The largest extra-adrenal cluster of chromaffin cells in mammals is the organ of Zuckerkandl. 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.
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. 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.
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 also stain yellow when treated with chromium salts), but their function is quite different and they are not derivatives of the neural crest.
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.
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. This upregulation of GRK2 is also accompanied by upregulation and increased production of the enzyme tyrosine hydroxylase, which is the catalyzes the rate limiting step of catecholamine synthesis.
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- Histology image: 14507loa – Histology Learning System at Boston University - "Endocrine System: adrenal gland, reticularis and medulla"
- Secretion Control in Adrenal Chromaffin Cells
- UC-San Diego Chromaffin Cell and Hypertension Research
- A Primer on Chromaffin Cells
- Rat Chromaffin cells primary cultures: Standardization and quality assessment for single-cell assays (a protocol)