The chromaffin cells are those that are located in the medulla of the adrenal glands. These glands, located at the top of each kidney, have an outer cortex that secretes steroid hormones and an inner medulla with chromaffin cells that act as a ganglion that secretes catecholamines.
Chromaffin cells, together with the sympathetic nervous system, are activated during the "fight or flight" response that occurs in fear, stress, exercise or conflict reactions and constitute, under these conditions, the main source of catecholamines that our body mobilizes.
Photograph of chromaffin cells using different microscopy methods (Source: Jhpbroeke via Wikimedia Commons)
In these reactions, the body prepares itself to develop maximum strength and maximum alertness. To do this, it increases cardiac work and blood pressure; generates coronary vasodilation and vasodilation of the skeletal muscle arterioles.
In the same sense, blood flow to the periphery and to the gastrointestinal system is reduced. Glucose is mobilized from the liver and the bronchi and pupils are dilated in a way that improves breathing and visual acuity for distant vision.
Representative diagram of the body's responses to stress. Stress can activate the autonomic sympathetic nerves in the adrenal medulla and promote the synthesis and release of catecholamines into the blood, which has downstream effects on the immune system (Source: Campos-Rodríguez R, Godínez-Victoria M, Abarca-Rojano E, Pacheco-Yépez J, Reyna-Garfias H, Barbosa-Cabrera RE, Drago-Serrano ME via Wikimedia Commons)
These reactions summarize the peripheral effect of catecholamines, especially epinephrine, which is the main secretion product of chromaffin cells. Responses are achieved through different receptors linked to various intracellular cascades. Four types of adrenergic receptors are known: α1, α2, ß1, and β2.
characteristics
The nervous system can be divided into two semi-independent systems:
- The somatic nervous system, which allows us to relate to the external environment and react to the conscious perception of sensory stimuli and
- The autonomic nervous system, which regulates the internal environment
Most of the autonomic sensory signals (from the autonomic nervous system) are not perceived in consciousness and autonomic control of motor activities is involuntary.
Scope of the autonomic nervous system (Source: Geo-Science-International via Wikimedia Commons)
Although the anatomical structure of both systems is similar, with sensory inputs and motor outputs, the autonomic system differs in that its output is through two sources of motor neurons, the sympathetic and the parasympathetic.
Furthermore, each motor output that projects to an effector has a chain of two neurons, one preganglionic and one postganglionic.
The bodies of the preganglionic neurons are in the brain stem and in the spinal cord. The bodies of postganglionic neurons are located peripherally in the autonomic ganglia.
Chromaffin cells in the adrenal medulla
The adrenal medulla is a modified sympathetic autonomic ganglion, since the sympathetic preganglionic fibers end up stimulating the chromaffin cells of this medulla. But these cells, instead of connecting with their target organs through axons, they do so through hormonal secretion.
Chromaffin cells secrete mainly epinephrine and small amounts of norepinephrine and dopamine. By discharging its secretion into the bloodstream, its effects are very wide and diverse, since it affects a large number of target organs.
Normally, the amount of catecholamines secreted is not very large, but in situations of stress, fear, anxiety, and profuse pain, increased stimulation of the sympathetic preganglionic endings causes large amounts of adrenaline to be secreted.
Histology
The adrenal medulla has its embryonic origin in the cells of the neural crest, from the last thoracic levels to the first lumbar. These migrate to the adrenal gland, where chromaffin cells are formed and the adrenal medulla is structured.
In the adrenal medulla, chromaffin cells are organized into short, intertwined cords of richly innervated cells (with abundant presence of nerve endings) that adjoin venous sinuses.
Chromaffin cells are large cells, which form short cords and are stained dark brown with chromaffin salts, from which they derive their name.
They are modified postganglionic cells, without dendrites or axons, that secrete catecholamines into the bloodstream when stimulated by preganglionic sympathetic cholinergic endings.
Two types of chromaffin cells can be distinguished. Some are the most abundant (90% of the total), they have large little dense cytosolic granules and are those that produce adrenaline.
The other 10% is represented by cells, with small, dense granules that produce norepinephrine. There are no histological differences between cells that produce epinephrine and those that produce dopamine.
Action mechanisms
The mechanisms of action of catecholamines released by chromaffin cells depend on the receptor to which they bind. At least four types of adrenergic receptors are known: α1, α2, ß1 and β2.
These receptors are G protein-linked metabotropic receptors, which have different intracellular second messenger mechanisms and whose effects can be stimulatory or inhibitory.
The α1 receptors are linked to a stimulatory G protein; the binding of epinephrine to the receptor decreases the affinity of the protein to GDP, thereby binding to GTP and becoming activated.
Representative diagram of the function of adrenergic receptors and their intracellular signaling mechanisms (Source: Sven Jähnichen. Partially translated by Mikael Häggström via Wikimedia Commons)
Activation of protein G stimulates the enzyme phospholipase C that generates inositol triphosphate (IP3), a second messenger that binds to intracellular calcium channels. This produces an increase in the internal calcium concentration and contraction of vascular smooth muscle is promoted.
The β1 receptors interact with a stimulating G protein that activates the enzyme adenylate cyclase, which produces cAMP as a second messenger, it activates a protein kinase that phosphorylates a calcium channel, the channel opens and calcium enters the muscle cell.
The ß2 receptors are linked to a G protein that, when activated, activates an adenylate cyclase that increases the concentration of cAMP. CAMP activates a protein kinase that phosphorylates a potassium channel that opens and lets out potassium, causing the cell to hyperpolarize and relax.
The α2 receptors are G-protein-linked receptors that also act through cAMP as a second messenger and decrease calcium entry into the cell by promoting the closure of calcium channels.
Features
The functions of chromaffin cells are related to the effects induced by catecholamines that they synthesize and release upon sympathetic preganglionic stimulation.
The sympathetic preganglionic fibers secrete acetylcholine, which acts through a nicotinic receptor.
This receptor is an ion channel and the binding of the receptor with acetylcholine promotes the release of the vesicles containing the catecholamines produced by the different chromaffin cells.
As a result, adrenaline and small amounts of norepinephrine and dopamine are secreted into the circulation, which are released and distributed through the bloodstream to reach target cells, which have adrenergic receptors.
In vascular smooth muscle, through an α1 receptor, epinephrine causes vasoconstriction by inducing smooth muscle contraction, contributing to the hypertensive effect of catecholamines.
Contraction of cardiac myocytes (cardiac muscle cells) due to adrenaline binding to β1 receptors increases the contraction force of the heart. These receptors are also located in the cardiac pacemaker and their final effect is to increase the heart rate.
The ß2 receptors are in the bronchial smooth muscle and in the smooth muscle of the coronary arteries, and epinephrine causes bronchodilation and coronary vasodilation, respectively.
Binding of epinephrine or norepinephrine to α2 receptors reduces the release of neurotransmitters from the presynaptic ganglionic endings where they are found. Dopamine causes renal vasodilation.
References
- Aunis, D. (1998). Exocytosis in chromaffin cells of the adrenal medulla. In International review of cytology (Vol. 181, pp. 213-320). Academic Press.
- Lumb, R., Tata, M., Xu, X., Joyce, A., Marchant, C., Harvey, N.,… & Schwarz, Q. (2018). Neuropilins guide preganglionic sympathetic axons and chromaffin cell precursors to establish the adrenal medulla. Development, 145 (21), dev162552.
- Borges, R., Gandía, L., & Carbone, E. (2018). Old and emerging concepts on adrenal chromaffin cell stimulus-secretion coupling.
- Wilson-Pauwels, L., Stewart, PA, & Akesson, EJ (Eds.). (1997). Autonomic nerves: Basic science, clinical aspects, case studies. PMPH USA.
- Jessell, TM, Kandel, ER, & Schwartz, JH (2000). Principles of neural science (No. 577.25 KAN).
- William, FG, & Ganong, MD (2005). Review of medical physiology. Printed in United States of America, Seventeenth Edition, Pp-781.