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Neuroscience Letters Mar 2023Disturbances that threaten homeostasis elicit activation of the sympathetic nervous system (SNS) and the adrenal medulla. The effectors discharge as a unit to drive...
Disturbances that threaten homeostasis elicit activation of the sympathetic nervous system (SNS) and the adrenal medulla. The effectors discharge as a unit to drive global and immediate changes in whole-body physiology. Descending sympathetic information is conveyed to the adrenal medulla via preganglionic splanchnic fibers. These fibers pass into the gland and synapse onto chromaffin cells, which synthesize, store, and secrete catecholamines and vasoactive peptides. While the importance of the sympatho-adrenal branch of the autonomic nervous system has been appreciated for many decades, the mechanisms underlying transmission between presynaptic splanchnic neurons and postsynaptic chromaffin cells have remained obscure. In contrast to chromaffin cells, which have enjoyed sustained attention as a model system for exocytosis, even the Ca sensors that are expressed within splanchnic terminals have not yet been identified. This study shows that a ubiquitous Ca-binding protein, synaptotagmin-7 (Syt7), is expressed within the fibers that innervate the adrenal medulla, and that its absence can alter synaptic transmission in the preganglionic terminals of chromaffin cells. The prevailing impact in synapses that lack Syt7 is a decrease in synaptic strength and neuronal short-term plasticity. Evoked excitatory postsynaptic currents (EPSCs) in Syt7 KO preganglionic terminals are smaller in amplitude than in wild-type synapses stimulated in an identical manner. Splanchnic inputs also display robust short-term presynaptic facilitation, which is compromised in the absence of Syt7. These data reveal, for the first time, a role for any synaptotagmin at the splanchnic-chromaffin cell synapse. They also suggest that Syt7 has actions at synaptic terminals that are conserved across central and peripheral branches of the nervous system.
Topics: Acetylcholine; Synaptotagmins; Splanchnic Nerves; Chromaffin Cells; Adrenal Medulla; Synapses
PubMed: 36796621
DOI: 10.1016/j.neulet.2023.137129 -
Irish Journal of Medical Science Feb 2016Pheochromocytomas are rare neuroendocrine tumors of the adrenal medulla that may present with protean manifestations. Surgical resection is the mainstay of therapy and... (Review)
Review
INTRODUCTION
Pheochromocytomas are rare neuroendocrine tumors of the adrenal medulla that may present with protean manifestations. Surgical resection is the mainstay of therapy and patients are at risk of significant hemodynamic and circulatory complications mainly attributable to catecholamine excess. The mainstay of medical therapy in order to optimize patients for surgery includes: alpha-blockers, beta-blockers, calcium channel blocker and other agents to achieve normal blood pressure, heart rate, as well as normal volume status. Understanding the pathophysiology of pheochromocytoma, the pharmacology of medications used, and recognizing postoperative complications will impact patient outcomes.
CONCLUSION
A multidisciplinary team approach is best throughout the perioperative period to prevent potential complications that arise. The hospital physician, intensivist, anesthetist and cardiovascular specialist play a pivotal role in the management of patients with pheochromocytoma. In addition to the pharmacologic and volume recommendations, a multidisciplinary discussion allows for seamless implementation of an organized plan of care.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Blood Pressure; Calcium Channel Blockers; Hemodynamics; Humans; Pheochromocytoma; Postoperative Complications
PubMed: 26650752
DOI: 10.1007/s11845-015-1383-5 -
The Journal of Histochemistry and... May 2022Secretogranin II (SgII) and III (SgIII) function within peptide hormone-producing cells and are involved in secretory granule formation. However, their function in...
Secretogranin II (SgII) and III (SgIII) function within peptide hormone-producing cells and are involved in secretory granule formation. However, their function in active amine-producing cells is not fully understood. In this study, we analyzed the expression profiles of SgII and SgIII in canine adrenal medulla and pheochromocytomas by immunohistochemical staining. In normal adrenal tissues, the intensity of coexpression of these two secretogranins (Sgs) differed from each chromaffin cell, although a complete match was not observed. The coexpression of vesicular monoamine transporter 2 (VMAT2) with SgIII was similar to that with chromogranin A, but there was a subpopulation of VMAT2-expressing cells that were negative or hardly detectable for SgII. These results are the first to indicate that there are distinct expression patterns for SgII and SgIII in adrenal chromaffin cells. Furthermore, the expression of these two Sgs varied in intensity among pheochromocytomas and did not necessarily correlate with clinical plasma catecholamine levels in patients. However, compared with SgIII, the expression of SgII was shown to be strong at the single-cell level in some tumor tissues. These findings provide a fundamental understanding of the expression differences between SgII and SgIII in normal adrenal chromaffin cells and pheochromocytomas.
Topics: Adrenal Gland Neoplasms; Animals; Chromaffin Cells; Chromogranins; Dogs; Humans; Pheochromocytoma; Secretogranin II
PubMed: 35400231
DOI: 10.1369/00221554221091000 -
Current Opinion in Oncology May 2019Over the last 20 years, the genetic landscape of adrenal tumours has been transformed by the identification of multiple susceptibility genes for the various tumour... (Review)
Review
PURPOSE OF REVIEW
Over the last 20 years, the genetic landscape of adrenal tumours has been transformed by the identification of multiple susceptibility genes for the various tumour types. We review these recent developments here, and describe current recommendations for genetic testing in patients with tumours of the adrenal medulla and extra-adrenal paraganglia or the adrenal cortex.
RECENT FINDINGS
Phaeochromocytomas (adrenal medulla tumours) and paragangliomas, aldosterone-producing adenomas, primary macronodular adrenal hyperplasia, primary pigmented nodular adrenocortical disease and adrenocortical carcinoma (adrenal cortex tumours) may all be caused by a germline mutation in a specific gene, regardless of the presence/absence of a family history or syndromic disease at initial diagnosis. Dedicated genetic testing is now indicated in all these conditions, and in patients with clinical features suggestive of a specific inherited disease.
SUMMARY
Genetic testing should be considered in all patients with adrenal tumours, and is crucial for correct management. The identification of a germline mutation in a susceptibility gene guides treatment in patients with adrenal cancer and will facilitate risk-adapted screening/surveillance protocols in mutation carriers.
Topics: Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Germ-Line Mutation; Humans; Paraganglioma; Pheochromocytoma
PubMed: 30985498
DOI: 10.1097/CCO.0000000000000525 -
Cureus Jun 2023A pheochromocytoma is an uncommon tumor that originates from the chromaffin cells of the adrenal medulla. Also, adrenal tissue not located in its typical position is...
A pheochromocytoma is an uncommon tumor that originates from the chromaffin cells of the adrenal medulla. Also, adrenal tissue not located in its typical position is referred to as ectopic adrenal tissue. It is relatively uncommon in adults and is usually asymptomatic. Therefore, a pheochromocytoma arising from ectopic adrenal tissue is even a rarer finding and presents as a unique diagnostic challenge. A 20-year-old man presented with vague abdominal pain, and upon imaging, a mass located behind the liver was initially discovered. Subsequently, it was identified as a mass growing in an ectopic adrenal gland. He underwent exploratory laparotomy and resection of the mass. A pheochromocytoma in an ectopic adrenal gland was confirmed by histopathology.
PubMed: 37425549
DOI: 10.7759/cureus.40068 -
Revista Espanola de Anestesiologia Y... Apr 2022Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Most adrenal pheochromocytomas secrete norepinephrine and...
Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Most adrenal pheochromocytomas secrete norepinephrine and epinephrine. Dopamine secreting pheochromocytomas are extremely rare and differs from classic pheochromocytomas in clinical features, posing a significant diagnostic challenge. A 41-year-old women presented to our emergency department because of acute flank colic pain and normotension. The screening abdominal computed tomography scan revealed a left adrenal mass. The laboratory test showed significantly increase in plasma dopamine and 24-h urine dopamine. During surgical removal the patient remained hypotensive requiring doses of norepinephrine. The patient presented significant hypertensive responde during direct laryngoscopy and intubation.
Topics: Adrenal Gland Neoplasms; Adult; Anesthetics; Dopamine; Female; Humans; Norepinephrine; Pheochromocytoma
PubMed: 35534387
DOI: 10.1016/j.redare.2020.12.009 -
The International Journal of... Aug 2016The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which... (Review)
Review
The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well.
Topics: Adrenal Glands; Animals; Catecholamines; Chromaffin Cells; Humans; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 26851510
DOI: 10.1016/j.biocel.2016.02.003 -
Anatomia, Histologia, Embryologia Sep 2021We performed 3D reconstruction of the microscopic structure of the adrenal medulla of the adult rats using serial histological sections with histochemical...
We performed 3D reconstruction of the microscopic structure of the adrenal medulla of the adult rats using serial histological sections with histochemical differentiation of adrenaline-storing (A) and noradrenaline-storing (NA) cells. Medulla volume is 1.18 ± 0.17 mm . Chromaffin tissue consists of 82.9 ± 2.6% of A and 17.1 ± 2.6% of NA cells. Cords of the chromaffinocytes run along the nerves in the adrenal cortex and form cones when merging with medulla bulk. There is no unambiguously greater prevalence of A cells over NA in the areas of the medulla bordering on the cortex as compared to deep layers of medulla. NA cells form a network of beams. Their concentration increases with distance from the entry site of the nerves and is maximal on the opposite side. This testifies to the fallacy of the point of view about the disordered distribution of NA cells in the medulla. Based on the polar asymmetric arrangement of the adrenal chromaffin tissue, if it is necessary to completely remove the medulla with the keeping or reimplantation of the cortex, the subcapsular cortex zone located on the pole opposite to the entrance of nerves should be chosen. In addition, comparable results in the stereological examination of the medulla can be obtained only if taking its areas similar in location. The pronounced relationship in the arrangement of A and NA cells with nerves clearly indicates that in vivo nerve factors play a key role in differentiation and stabilization of the A and NA cells phenotypes.
Topics: Adrenal Glands; Adrenal Medulla; Animals; Epinephrine; Imaging, Three-Dimensional; Norepinephrine; Rats
PubMed: 34145614
DOI: 10.1111/ahe.12720 -
Frontiers in Endocrinology 2018Pheochromocytomas and paragangliomas (PCCs/PGLs) are rare commonly benign neuroendocrine tumors that share pathology features and clinical behavior in many cases. While... (Review)
Review
Pheochromocytomas and paragangliomas (PCCs/PGLs) are rare commonly benign neuroendocrine tumors that share pathology features and clinical behavior in many cases. While PCCs are chromaffin-derived tumors that arise within the adrenal medulla, PGLs are neural-crest-derived tumors that originate at the extraadrenal paraganglia. Pheochromocytoma-paraganglioma (PPGL) syndromes are rapidly evolving entities in endocrinology and oncology. Discoveries over the last decade have significantly improved our understanding of the disease. These include the finding of new hereditary forms of PPGL and their associated susceptibility genes. Additionally, the availability of new functional imaging tools and advances in targeted radionuclide therapy have improved diagnostic accuracy and provided us with new therapeutic options. In this review article, we present the most recent advances in this field and provide an update of the biochemical classification that further reflects our understanding of the disease.
PubMed: 30538672
DOI: 10.3389/fendo.2018.00515 -
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