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Pflugers Archiv : European Journal of... Jan 2018The chromaffin cells (CCs) of the adrenal medulla play a key role in the control of circulating catecholamines to adapt our body function to stressful conditions. A huge...
The chromaffin cells (CCs) of the adrenal medulla play a key role in the control of circulating catecholamines to adapt our body function to stressful conditions. A huge research effort over the last 35 years has converted these cells into the Escherichia coli of neurobiology. CCs have been the testing bench for the development of patch-clamp and amperometric recording techniques and helped clarify most of the known molecular mechanisms that regulate cell excitability, Ca signals associated with secretion, and the molecular apparatus that regulates vesicle fusion. This special issue provides a state-of-the-art on the many well-known and unsolved questions related to the molecular processes at the basis of CC function. The issue is also the occasion to highlight the seminal work of Antonio G. García (Emeritus Professor at UAM, Madrid) who greatly contributed to the advancement of our present knowledge on CC physiology and pharmacology. All the contributors of the present issue are distinguished scientists who are either staff members, external collaborators, or friends of Prof. García.
Topics: Adrenal Medulla; Animals; Chromaffin Granules; Humans; Signal Transduction
PubMed: 29110079
DOI: 10.1007/s00424-017-2082-z -
Frontiers in Endocrinology 2022The adrenal medulla plays a critical role in mammalian homeostasis and the stress response. It is populated by clustered chromaffin cells that secrete epinephrine or...
The adrenal medulla plays a critical role in mammalian homeostasis and the stress response. It is populated by clustered chromaffin cells that secrete epinephrine or norepinephrine along with peptides into the bloodstream affecting distant target organs. Despite been heavily studied, the central control of adrenal medulla and spatiotemporal responsiveness remains poorly understood. For this work, we continuously monitored the electrical activity of individual adrenomedullary chromaffin cells in the living anesthetized rat using multielectrode arrays. We measured the chromaffin cell activity under basal and physiological stress conditions and characterized the functional micro-architecture of the adrenal medulla. Under basal conditions, chromaffin cells fired action potentials with frequencies between ~0.2 and 4 Hz. Activity was almost completely driven by sympathetic inputs coming through the splanchnic nerve. Chromaffin cells were organized into independent local networks in which cells fired in a specific order, with latencies from hundreds of microseconds to a few milliseconds. Electrical stimulation of the splanchnic nerve evoked almost exactly the same spatiotemporal firing patterns that occurred spontaneously. Hypoglycemic stress, induced by insulin administration resulted in increased activity of a subset of the chromaffin cells. In contrast, respiratory arrest induced by lethal anesthesia resulted in an increase in the activity of virtually all chromaffin cells before cessation of all activity. These results suggest a stressor-specific activation of adrenomedullary chromaffin cell networks and revealed a surprisingly complex electrical organization that likely reflects the dynamic nature of the adrenal medulla's neuroendocrine output during basal conditions and during different types of physiological stress.
Topics: Adrenal Medulla; Animals; Chromaffin Cells; Epinephrine; Mammals; Norepinephrine; Rats; Splanchnic Nerves
PubMed: 35795145
DOI: 10.3389/fendo.2022.875865 -
British Heart Journal Apr 1953
Topics: Adrenal Medulla; Brain Stem Neoplasms; Neoplasms; Paraganglioma; Pheochromocytoma
PubMed: 13042003
DOI: 10.1136/hrt.15.2.241 -
Stem cells, evolutionary aspects and pathology of the adrenal medulla: A new developmental paradigm.Molecular and Cellular Endocrinology Dec 2020The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the... (Review)
Review
The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation.
Topics: Adrenal Gland Diseases; Adrenal Medulla; Animals; Biological Evolution; Cell Differentiation; Humans; Neural Crest; Stem Cells
PubMed: 32818585
DOI: 10.1016/j.mce.2020.110998 -
IUBMB Life Apr 2020Synaptic neurotransmission at the splanchnic nerve-chromaffin cell synapse is a chief element of the stimulus-secretion coupling in the adrenal medullary tissue,... (Review)
Review
Synaptic neurotransmission at the splanchnic nerve-chromaffin cell synapse is a chief element of the stimulus-secretion coupling in the adrenal medullary tissue, managing and regulating the secretion of catecholamines. Making the state of play more intricate than initially envisioned, the synaptic vesicles of nerve terminals innervating the medulla contain various compounds, including various neurotransmitters and neuropeptides. Under basal conditions associated with a low splanchnic nerve discharge rate, neurotransmission is ensured by the synaptic release of the primary neurotransmitter acetylcholine (ACh). Under sustained and repetitive stimulations of the splanchnic nerve, as triggered in response to stressors, the synaptic release of neuropeptides, such as the pituitary adenylate cyclase-activating polypeptide PACAP, supplants ACh release. The anatomical and functional changes that occur presynaptically at the preganglionic splanchnic nerve, combined with changes occurring postsynaptically at nicotinic acetylcholine receptors (nAChRs), confer the adrenomedullary synapses a solid and persistent aptitude to functional remodeling, from birth to aging. The present review focuses on the composite cholinergic and noncholinergic nature of neurotransmission occurring at the splanchnic nerve-chromaffin cell synapse and its remodeling in response to physiological or pathological stimuli.
Topics: Acetylcholine; Adrenal Medulla; Animals; Chromaffin Cells; Humans; Neuropeptides; Neurotransmitter Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Splanchnic Nerves; Synapses; Synaptic Transmission
PubMed: 31301221
DOI: 10.1002/iub.2117 -
Physiological Reports Sep 2016Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions of the sympathetic splanchnic...
Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions of the sympathetic splanchnic nerve. Upon synaptic stimulation, the adrenal medulla releases the catecholamines, epinephrine, and norepinephrine into the suprarenal vein for circulation throughout the body. Under sympathetic tone, catecholamine release is modest. However, upon activation of the sympathoadrenal stress reflex, and increased splanchnic firing, adrenal catecholamine output increases dramatically. Moreover, specific stressors can preferentially increase release of either epinephrine (i.e., hypoglycemia) or norepinephrine (i.e., cold stress). The mechanism for this stressor-dependent segregated release of catecholamine species is not yet fully understood. We tested the hypothesis that stimulation of either division of the splanchnic selects for epinephrine over norepinephrine release. We introduce an ex vivo rat preparation that maintains native splanchnic innervation of the adrenal gland and we document experimental advantages and limitations of this preparation. We utilize fast scanning cyclic voltammetry to detect release of both epinephrine and norepinephrine from the adrenal medulla, and report that epinephrine and norepinephrine release are regulated spatially and in a frequency-dependent manner. We provide data to show that epinephrine is secreted preferentially from the periphery of the medulla and exhibits a higher threshold and steeper stimulus-secretion function than norepinephrine. Elevated stimulation of the whole nerve specifically enhances epinephrine release from the peripheral medulla. Our data further show that elimination of either division from stimulation greatly attenuated epinephrine release under elevated stimulation, while either division alone can largely support norepinephrine release.
Topics: Adrenal Medulla; Animals; Catecholamines; Chromaffin Cells; Electric Stimulation; Epinephrine; Norepinephrine; Rats; Rats, Sprague-Dawley; Splanchnic Nerves
PubMed: 27597763
DOI: 10.14814/phy2.12898 -
Journal of Anatomy Oct 1993The adrenal medulla of mammals has a heterogeneous population of cells. In adults most are epithelial cells containing a particular type of cytoplasmic granule. Based on... (Review)
Review
The adrenal medulla of mammals has a heterogeneous population of cells. In adults most are epithelial cells containing a particular type of cytoplasmic granule. Based on a variety of cytochemical and ultrastructural studies it is now accepted that 2 different adrenal medullary chromaffin cell types can be distinguished, i.e. noradrenaline (NA) and adrenaline (A) synthesising and storing cells. Other cell types present in the adrenal medulla include neuronal elements comprising either cell bodies or nerve fibres entering from outside the gland (extrinsic innervation). It is assumed that adrenal medullary cells have a limited life span, i.e. they are replaced after a certain period. Data on this replacement process are scarce. Recently, we initiated an investigation into this question using cytochemical procedures that enable the detection of DNA duplication to measure mitotic activity in individual cells. Female Sprague-Dawley rats aged 22-36 wk received a single i.p. injection of BrdU or BrdU was administered continuously via an implanted mini-osmotic pump. Cell nuclei that had incorporated BrdU were demonstrated using an indirect immunoperoxidase staining technique. At 1 h after a single injection, 0.46 +/- 0.07% of the adrenal medullary (chromaffin) cells were labelled. This increased to 0.77 +/- 0.08% after 12 h with no further increase during the next 7-8 d. With continuous infusion of BrdU the fraction of labelled cells increased gradually to about 40% after 73 d (the longest period studied). These results show that in adult rats adrenal medullary cells are able to divide, although at a slow rate (renewal rate of about 1%/day).
Topics: Adrenal Medulla; Animals; Cell Division; Chromaffin System; DNA; Epinephrine; Female; Fluorescent Antibody Technique; Kinetics; Norepinephrine; Rats; Rats, Sprague-Dawley
PubMed: 8300419
DOI: No ID Found -
Journal of Applied Physiology... Oct 2012Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit... (Review)
Review
Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute to sympathetic activation by CIH. Studies on rodents showed that CIH augments the carotid body response to hypoxia and attenuates the carotid baroreceptor response to increased sinus pressures. Processing of afferent information from chemoreceptors at the central nervous system is also facilitated by CIH. Adult and neonatal rats exposed to CIH exhibit augmented catecholamine secretion from the adrenal medulla. Adrenal demedullation prevents the elevation of circulating catecholamines in CIH-exposed rodents. Reactive oxygen species (ROS)-mediated signaling is emerging as the major cellular mechanism triggering sympatho-adrenal activation by CIH. Molecular mechanisms underlying increased ROS generation by CIH seem to involve transcriptional dysregulation of genes encoding pro-and antioxidant enzymes by hypoxia-inducible factor-1 and -2, respectively.
Topics: Adrenal Medulla; Animals; Apnea; Humans; Hypoxia; Sympathetic Nervous System
PubMed: 22723632
DOI: 10.1152/japplphysiol.00444.2012 -
Scientific Reports Feb 2021Plasma noradrenaline levels increase with aging, and this could contribute to the sympathetic overactivity that is associated with essential hypertension and the...
Plasma noradrenaline levels increase with aging, and this could contribute to the sympathetic overactivity that is associated with essential hypertension and the metabolic syndrome. The underlying cause of this rise in noradrenaline is unknown, but a clue may be that mercury increases noradrenaline output from the adrenal medulla of experimental animals. We therefore determined the proportion of people from 2 to 104 years of age who had mercury in their adrenal medulla. Mercury was detected in paraffin sections of autopsied adrenal glands using two methods of elemental bioimaging, autometallography and laser ablation-inductively coupled plasma-mass spectrometry. Mercury first appeared in cells of the adrenal medulla in the 21-40 years group, where it was present in 52% of samples, and increased progressively in frequency in older age groups, until it was detected in 90% of samples from people aged over 80 years. In conclusion, the proportion of people having mercury in their adrenal medulla increases with aging. Mercury could alter the metabolism of catecholamines in the adrenal medulla that leads to the raised levels of plasma noradrenaline in aging. This retrospective autopsy study was not able to provide a definitive link between adrenal mercury, noradrenaline levels and hypertension, but future functional human and experimental studies could provide further evidence for these associations.
Topics: Adolescent; Adrenal Medulla; Adult; Aged; Aged, 80 and over; Aging; Child; Child, Preschool; Female; Humans; Hypertension; Mercury; Middle Aged; Norepinephrine; Retrospective Studies; Young Adult
PubMed: 33536525
DOI: 10.1038/s41598-021-82483-y -
Psychoneuroendocrinology Sep 2020The gut microbiota produces metabolites that are an integral part of the metabolome and, as such, of the host physiology. Changes in gut microbiota metabolism could...
BACKGROUND AND AIMS
The gut microbiota produces metabolites that are an integral part of the metabolome and, as such, of the host physiology. Changes in gut microbiota metabolism could therefore contribute to pathophysiological processes. We showed previously that a chronic and moderate overproduction of indole from tryptophan in male individuals of the highly stress-sensitive F344 rat strain induced anxiety-like and helplessness behaviors. The aim of the present study was to extend the scope of these findings by investigating whether emotional behaviors of male mice that are moderately stress-sensitive but chronically exposed to environmental stressors would also be affected by indole.
METHODS
We colonized germ-free male C3H/HeN mice with a wild-type indole-producing Escherichia coli strain, or with the non-indole producing mutant. Gnotobiotic mice were subjected to an unpredictable chronic mild stress procedure, then to a set of tests aimed at assessing anxiety-like (novelty and elevated plus maze tests) and depression-like behaviors (coat state, splash, nesting, tail suspension and sucrose tests). Results of the individual tests were aggregated into a common z-score to estimate the overall emotional response to chronic mild stress and chronic indole production. We also carried out biochemical and molecular analyses in gut mucosa, plasma, brain hippocampus and striatum, and adrenal glands, to examine biological correlates that are usually associated with stress, anxiety and depression.
RESULTS
Chronic mild stress caused coat state degradation and anhedonia in both indole-producing and non-indole producing mice, but it did not influence behaviors in the other tests. Chronic indole production did not influence mice behavior when tests were considered individually, but it increased the overall emotionality z-score, specifically in mice under chronic mild stress. Interestingly, in the same mice, indole induced a dramatic increase of the expression of the adrenomedullary Pnmt gene, which is involved in catecholamine biosynthesis. By contrast, systemic tryptophan bioavailability, brain serotonin and dopamine levels and turnover, as well as expression of gut and brain genes involved in cytokine production and tryptophan metabolism along the serotonin and kynurenine pathways, remained similar in all mice.
CONCLUSIONS
Chronic indole production by the gut microbiota increased the vulnerability of male mice to the adverse effects of chronic mild stress on emotional behaviors. It also targeted catecholamine biosynthetic pathway of the adrenal medulla, which plays a pivotal role in body's physiological adaptation to stressful events. Future studies will aim to investigate the action mechanisms responsible for these effects.
Topics: Adrenal Medulla; Animals; Behavior, Animal; Chronic Disease; Emotions; Gastrointestinal Microbiome; Indoles; Male; Mice; Mice, Inbred C3H; Stress, Psychological; Time Factors
PubMed: 32569990
DOI: 10.1016/j.psyneuen.2020.104750