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Physiological Reviews Jul 1997The stress response in teleost fish shows many similarities to that of the terrestrial vertebrates. These concern the principal messengers of the... (Review)
Review
The stress response in teleost fish shows many similarities to that of the terrestrial vertebrates. These concern the principal messengers of the brain-sympathetic-chromaffin cell axis (equivalent of the brain-sympathetic-adrenal medulla axis) and the brain-pituitary-interrenal axis (equivalent of the brain-pituitary-adrenal axis), as well as their functions, involving stimulation of oxygen uptake and transfer, mobilization of energy substrates, reallocation of energy away from growth and reproduction, and mainly suppressive effects on immune functions. There is also growing evidence for intensive interaction between the neuroendocrine system and the immune system in fish. Conspicuous differences, however, are present, and these are primarily related to the aquatic environment of fishes. For example, stressors increase the permeability of the surface epithelia, including the gills, to water and ions, and thus induce systemic hydromineral disturbances. High circulating catecholamine levels as well as structural damage to the gills and perhaps the skin are prime causal factors. This is associated with increased cellular turnover in these organs. In fish, cortisol combines glucocorticoid and mineralocorticoid actions, with the latter being essential for the restoration of hydromineral homeostasis, in concert with hormones such as prolactin (in freshwater) and growth hormone (in seawater). Toxic stressors are part of the stress literature in fish more so than in mammals. This is mainly related to the fact that fish are exposed to aquatic pollutants via the extensive and delicate respiratory surface of the gills and, in seawater, also via drinking. The high bioavailability of many chemicals in water is an additional factor. Together with the variety of highly sensitive perceptive mechanisms in the integument, this may explain why so many pollutants evoke an integrated stress response in fish in addition to their toxic effects at the cell and tissue levels. Exposure to chemicals may also directly compromise the stress response by interfering with specific neuroendocrine control mechanisms. Because hydromineral disturbance is inherent to stress in fish, external factors such as water pH, mineral composition, and ionic calcium levels have a significant impact on stressor intensity. Although the species studied comprise a small and nonrepresentative sample of the almost 20,000 known teleost species, there are many indications that the stress response is variable and flexible in fish, in line with the great diversity of adaptations that enable these animals to live in a large variety of aquatic habitats.
Topics: Animals; Chromaffin Cells; Energy Metabolism; Fish Diseases; Fishes; Hypothalamus; Immune System; Kidney; Neurotransmitter Agents; Pituitary Gland; Reproduction; Stress, Physiological; Sympathetic Nervous System
PubMed: 9234959
DOI: 10.1152/physrev.1997.77.3.591 -
Cancer Cell Nov 2020Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive...
Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Cell Differentiation; Cell Proliferation; Chromaffin Cells; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Neuroblastoma; Phenotype; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 32946775
DOI: 10.1016/j.ccell.2020.08.014 -
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 -
Mechanisms of Development 2013Ten years of research within the DFG-funded Collaborative Research Grant SFB 488 at the University of Heidelberg have added many new facets to our understanding of... (Review)
Review
Ten years of research within the DFG-funded Collaborative Research Grant SFB 488 at the University of Heidelberg have added many new facets to our understanding of chromaffin cell development. Glucocorticoid signaling is no longer the key for understanding the determination of the chromaffin phenotype, yet a novel role has been attributed to glucocorticoids: they are essential for the postnatal maintenance of adrenal and extra-adrenal chromaffin cells. Transcription factors, as, e.g. MASH1 and Phox2B, have similar, but also distinct functions in chromaffin and sympathetic neuronal development, and BMP-4 not only induces sympathoadrenal (SA) cells at the dorsal aorta and within the adrenal gland, but also promotes chromaffin cell maturation. Chromaffin cells and sympathetic neurons share a common progenitor in the dorsal neural tube (NT) in vivo, as revealed by single cell electroporations into the dorsal NT. Thus, specification of chromaffin cells is likely to occur after cell emigration either during migration or close to colonization of the target regions. Mechanisms underlying the specification of chromaffin cells vs. sympathetic neurons are currently being explored.
Topics: Adrenal Glands; Basic Helix-Loop-Helix Transcription Factors; Bone Morphogenetic Protein 4; Cell Differentiation; Chromaffin Cells; Gene Expression Regulation, Developmental; Glucocorticoids; Homeodomain Proteins; Humans; Neural Crest; Neurogenesis; Neurons; Signal Transduction; Transcription Factors
PubMed: 23220335
DOI: 10.1016/j.mod.2012.11.004 -
Pflugers Archiv : European Journal of... Jan 2018Vesicle fusion is elementary for intracellular trafficking and release of signal molecules, thus providing the basis for diverse forms of intercellular communication... (Review)
Review
Vesicle fusion is elementary for intracellular trafficking and release of signal molecules, thus providing the basis for diverse forms of intercellular communication like hormonal regulation or synaptic transmission. A detailed characterization of the mechanisms underlying exocytosis is key to understand how the nervous system integrates information and generates appropriate responses to stimuli. The machinery for vesicular release employs common molecular players in different model systems including neuronal and neuroendocrine cells, in particular members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein family, Sec1/Munc18-like proteins, and other accessory factors. To achieve temporal precision and speed, excitable cells utilize specialized regulatory proteins like synaptotagmin and complexin, whose interplay putatively synchronizes vesicle fusion and enhances stimulus-secretion coupling. In this review, we aim to highlight recent progress and emerging views on the molecular mechanisms, by which constitutively forming SNAREpins are organized in functional, tightly regulated units for synchronized release. Specifically, we will focus on the role of vesicle associated membrane proteins, also referred to as vesicular SNAREs, in fusion and rapid cargo discharge. We will further discuss the functions of SNARE regulators during exocytosis and focus on chromaffin cell as a model system of choice that allows for detailed structure-function analyses and direct measurements of vesicle fusion under precise control of intracellular [Ca]i.
Topics: Animals; Chromaffin Cells; Exocytosis; Humans; Membrane Fusion; SNARE Proteins
PubMed: 28887593
DOI: 10.1007/s00424-017-2066-z -
Pflugers Archiv : European Journal of... Jan 2018Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified in hypothalamus, based on its ability to elevate cyclic AMP in the anterior pituitary.... (Review)
Review
Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified in hypothalamus, based on its ability to elevate cyclic AMP in the anterior pituitary. PACAP has been identified as the adrenomedullary neurotransmitter in stress through a combination of ex vivo, in vivo, and in cellula experiments over the past two decades. PACAP causes catecholamine secretion, and activation of catecholamine biosynthetic enzymes, during episodes of stress in mammals. Features of PACAP signaling allowing stress transduction at the splanchnicoadrenomedullary synapse have yielded insights into the contrasting roles of acetylcholine's and PACAP's actions as first messengers at the chromaffin cell, via differential release at low and high rates of splanchnic nerve firing, and differential signaling pathway engagement leading to catecholamine secretion and chromaffin cell gene transcription. Secretion stimulated by PACAP, via calcium influx independent of action potential generation, is under active investigation in several laboratories both at the chromaffin cell and within autonomic ganglia of both the parasympathetic and sympathetic nervous systems. PACAP is a neurotransmitter important in stress transduction in the central nervous system as well, and is found at stress-transduction nuclei in brain including the paraventricular nucleus of hypothalamus, the amygdala and extended amygdalar nuclei, and the prefrontal cortex. The current status of PACAP as a master regulator of stress signaling in the nervous system derives fundamentally from the establishment of its role as the splanchnicoadrenomedullary transmitter in stress. Experimental elucidation of PACAP action at this synapse remains at the forefront of understanding PACAP's role in stress signaling throughout the nervous system.
Topics: Animals; Catecholamines; Chromaffin Cells; Humans; Pituitary Adenylate Cyclase-Activating Polypeptide; Stress, Physiological; Synaptic Transmission
PubMed: 28965274
DOI: 10.1007/s00424-017-2062-3 -
Pflugers Archiv : European Journal of... Apr 2014Besides controlling a wide variety of cell functions, T-type channels have been shown to regulate neurotransmitter release in peripheral and central synapses and... (Review)
Review
Besides controlling a wide variety of cell functions, T-type channels have been shown to regulate neurotransmitter release in peripheral and central synapses and neuroendocrine cells. Growing evidence over the last 10 years suggests a key role of Cav3.2 and Cav3.1 channels in controlling basal neurosecretion near resting conditions and sustained release during mild stimulations. In some cases, the contribution of low-voltage-activated (LVA) channels is not directly evident but requires either the activation of coupled presynaptic receptors, block of ion channels, or chelation of metal ions. Concerning the coupling to the secretory machinery, T-type channels appear loosely coupled to neurotransmitter and hormone release. In neurons, Cav3.2 and Cav3.1 channels mainly control the asynchronous appearance of "minis" [miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory postsynaptic currents (mEPSCs)]. The same loose coupling is evident from membrane capacity and amperometric recordings in chromaffin cells and melanotropes where the low-threshold-driven exocytosis possesses the same linear Ca(2+) dependence of the other voltage-gated Ca(2+) channels (Cav1 and Cav2) that is strongly attenuated by slow calcium buffers. The intriguing issue is that, despite not expressing a consensus "synprint" site, Cav3.2 channels do interact with syntaxin 1A and SNAP-25 and, thus, may form nanodomains with secretory vesicles that can be regulated at low voltages. In this review, we discuss all the past and recent issues related to T-type channel-secretion coupling in neurons and neuroendocrine cells.
Topics: Animals; Calcium Channels, T-Type; Chromaffin Cells; Exocytosis; Humans; Neurons; Neurotransmitter Agents; Synapses; Synaptic Transmission
PubMed: 24595475
DOI: 10.1007/s00424-014-1489-z -
Frontiers in Endocrinology 2022During embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland the "bridge" transient stage, according...
During embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland the "bridge" transient stage, according to recent functional experiments and single cell data from humans and mice. However, currently existing data do not resolve the finest heterogeneity of developing chromaffin populations. Here we took advantage of deep SmartSeq2 transcriptomic sequencing to expand our collection of individual cells from the developing murine sympatho-adrenal anlage and uncover the microheterogeneity of embryonic chromaffin cells and their corresponding developmental paths. We discovered that SCPs on the splachnic nerve show a high degree of microheterogeneity corresponding to early biases towards either Schwann or chromaffin terminal fates. Furthermore, we found that a post-"bridge" population of developing chromaffin cells gives rise to persisting oxygen-sensing chromaffin cells and the two terminal populations (adrenergic and noradrenergic) diverging differentiation paths. Taken together, we provide a thorough identification of novel markers of adrenergic and noradrenergic populations in developing adrenal glands and report novel differentiation paths leading to them.
Topics: Adrenal Glands; Adrenergic Agents; Animals; Cell Differentiation; Chromaffin Cells; Female; Humans; Mice; Norepinephrine; Oxygen; Pregnancy
PubMed: 36237181
DOI: 10.3389/fendo.2022.1020000 -
Cell Calcium 2012Voltage gated Ca(2+) channels are effective voltage sensors of plasma membrane which convert cell depolarizations into Ca(2+) signaling. The chromaffin cells of the... (Review)
Review
Voltage gated Ca(2+) channels are effective voltage sensors of plasma membrane which convert cell depolarizations into Ca(2+) signaling. The chromaffin cells of the adrenal medulla utilize a large number of Ca(2+) channel types to drive the Ca(2+)-dependent release of catecholamines into blood circulation, during normal or stress-induced conditions. Some of the Ca(2+) channels expressed in chromaffin cells (L, N, P/Q, R and T), however, do not control only vesicle fusion and catecholamine release. They also subserve a variety of key activities which are vital for the physiological and pathological functioning of the cell, like: (i) shaping the action potentials of electrical oscillations driven either spontaneously or by ACh stimulation, (ii) controlling the action potential frequency of tonic or bursts firing, (iii) regulating the compensatory and excess endocytosis following robust exocytosis and (iv) driving the remodeling of Ca(2+) signaling which occurs during stressors stimulation. Here, we will briefly review the well-established properties of voltage-gated Ca(2+) channels accumulated over the past three decades focusing on the most recent discoveries on the role that L- (Cav1.2, Cav1.3) and T-type (Cav3.2) channels play in the control of excitability, exocytosis and endocytosis of chromaffin cells in normal and stress-mimicking conditions.
Topics: Action Potentials; Animals; Calcium Channels, L-Type; Calcium Channels, T-Type; Calcium Signaling; Catecholamines; Chromaffin Cells; Endocytosis; Exocytosis; Humans; Receptor Cross-Talk
PubMed: 22317919
DOI: 10.1016/j.ceca.2012.01.005 -
Histochemistry and Cell Biology Aug 2010Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis,... (Review)
Review
Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis, neurotransmitter-containing vesicles dock to the target membrane. In electron micrographs of neurons and neuroendocrine cells, like chromaffin cells many synaptic vesicles (SVs) and large dense-core vesicles (LDCVs) are docked. For many years the molecular identity of the morphologically docked state was unknown. Recently, we resolved the minimal docking machinery in adrenal medullary chromaffin cells using embryonic mouse model systems together with electron-microscopic analyses and also found that docking is controlled by the sub-membrane filamentous (F-)actin. Currently it is unclear if the same docking machinery operates in synapses. Here, I will review our docking assay that led to the identification of the LDCV docking machinery in chromaffin cells and also discuss whether identical docking proteins are required for SV docking in synapses.
Topics: Animals; Chromaffin Cells; Hormones; Mice; Neurotransmitter Agents; Protein Binding; Secretory Vesicles; Synapses
PubMed: 20577884
DOI: 10.1007/s00418-010-0719-5