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This historical review focuses on the evolution of the knowledge accumulated during the last two centuries on the biology of the adrenal medulla gland and its chromaffin cells (CCs). The review emerged in the context of a series of meetings that started on the Spanish island of Ibiza in 1982 with the name of the International Symposium on Chromaffin Cell Biology (ISCCB). Hence, the review is divided into two periods namely, before 1982 and from this year to 2022, when the 21st ISCCB meeting was just held in Hamburg, Germany. The first historical period extends back to 1852 when Albert Kölliker first described the fine structure and function of the adrenal medulla. Subsequently, the adrenal staining with chromate salts identified the CCs; this was followed by the establishment of the embryological origin of the adrenal medulla, and the identification of adrenaline-storing vesicles. By the end of the nineteenth century, the basic morphology, histochemistry, and embryology of the adrenal gland were known. The twentieth century began with breakthrough findings namely, the experiment of Elliott suggesting that adrenaline was the sympathetic neurotransmitter, the isolation of pure adrenaline, and the deciphering of its molecular structure and chemical synthesis in the laboratory. In the 1950s, Blaschko isolated the catecholamine-storing vesicles from adrenal medullary extracts. This switched the interest in CCs as models of sympathetic neurons with an explosion of studies concerning their functions, i.e., uptake of catecholamines by chromaffin vesicles through a specific coupled transport system; the identification of several vesicle components in addition to catecholamines including chromogranins, ATP, opioids, and other neuropeptides; the calcium-dependence of the release of catecholamines; the underlying mechanism of exocytosis of this release, as indicated by the co-release of proteins; the cross-talk between the adrenal cortex and the medulla; and the emission of neu

Paragangliomas of the jugular foramen are rare. They may present with symptoms of compression of the glossopharyngeal or vagus nerves, or due to secretion of catecholamines from chromaffin cells within the tumour. This case describes a rare presentation of glomus tumour. A 67-year-old patient presented with a 2-month history of right-sided tongue swelling. She was found to have an obvious swelling on the right side of the tongue but no obvious weakness or fasciculation on initial examination. Ultrasound confirmed diffuse muscle swelling, but no lesion within the tongue. Magnetic resonance imaging of the neck revealed an ipsilateral glomus jugulare tumour that extended to the hypoglossal canal, and had resulted in ipsilateral denervation pseudohypertrophy of the lingual muscles. This paper reviews presentation of glomus jugulare tumours and contributes a novel presentation of a rare entity.Copyright © 2018 International Association of Oral and Maxillofacial Surgeons

Sympathetic neurons and adrenal chromaffin cells originate from a common precursor, the neural crest-derived sympathoadrenal (SA) progenitor cell. Specification of trunk neural crest cells into SA progenitor cells is under the influence of bone morphogenetic proteins (BMPs) produced from the wall of the dorsal aorta. SA progenitor cells then further differentiate into either sympathetic neurons of the sympathetic ganglia or chromaffin cells in the adrenal medulla. However, the mechanism underlying the segregation of chromaffin and neuronal cell fates remain unknown and the time course of SA segregation and regulation of cell fate is poorly understood. To discover novel regulators, and to have a broader view of the transcriptional networks involved in the segregation events, large scale gene screening is required. Isolation of sympathetic neuroblasts and adrenal chromaffin precursor cells for molecular studies, however, is challenging, as they are hard to discriminate during early development. Therefore, the aims of this study were to 1), identify effective marker(s) for early discrimination of neuroblasts and chromaffin precursor cells in order to 2), investigate their patterns of proliferation and differentiation and 3), develop an isolation method by fluorescence-activated cell sorting (FACS) for the two cell types, and finally 4), perform a comparative transcriptomic analysis by using RNA sequencing (RNA-seq) to identify candidate regulator genes that control fate determination of developing adrenal chromaffin cells and sympathetic neuroblasts. The temporal and spatial expression patterns of tyrosine hydroxylase (TH) and cocaine and amphetamine regulated transcript (CART) were first analysed by quadruple-label immunofluorescence. The proliferative behaviour of SA cells and their derivatives were also analysed. Our data showed that sympathetic neuroblasts and chromaffin precursor cells could be discriminated as early as E12.5 by differences in the intensity of TH

Immunohistochemistry has been used to examine the distribution of selected phospholipase C (PLC) isozymes within the adrenal medulla of the rat. PLCbeta isozymes were expressed at moderate levels in the chromaffin cells but more strongly in association with ganglion cell clusters. PLCbeta2 and PLCbeta3 staining of clusters did not overlap suggesting selective PLC isozyme expression in two distinct ganglionic types. The distribution of PLCbeta4 immunoreactivity was very similar to PLCbeta3 with the strongest staining observed in the same cell clusters. Antibodies to PLCbeta1 labelled multiple bands on Western blots and were not therefore used for immunohistochemistry. The chromaffin cells were also immunoreactive for PLCgamma1, although the strongest staining with this antibody was seen in cells surrounding large sinus vessels. PLCdelta1 and PLCdelta2 had quite distinct distributions, with the former selectively localized to an endothelial cell population surrounding the chromaffin cells. This observation was supported by experiments on isolated bovine adrenal medullary cells where PLCdelta1 expression was lost when the cell preparation was enriched for chromaffin cells. Antibodies to PLCdelta2 labelled a network of nerve fibres throughout the medulla and clusters of ganglion cells located primarily at the medullary-cortical boundary. PLCdelta2 immunoreactivity was also present in nerve fibres within the adrenal capsule where it appeared to be co-localized with PLCbeta4 staining. © 2005 Elsevier Ireland Ltd. All rights reserved.

Immunohistochemistry has been used to examine the distribution of selected phospholipase C (PLC) isozymes within the adrenal medulla of the rat. PLCbeta isozymes were expressed at moderate levels in the chromaffin cells but more strongly in association with ganglion cell clusters. PLCbeta2 and PLCbeta3 staining of clusters did not overlap suggesting selective PLC isozyme expression in two distinct ganglionic types. The distribution of PLCbeta4 immunoreactivity was very similar to PLCbeta3 with the strongest staining observed in the same cell clusters. Antibodies to PLCbeta1 labelled multiple bands on Western blots and were not therefore used for immunohistochemistry. The chromaffin cells were also immunoreactive for PLCgamma1, although the strongest staining with this antibody was seen in cells surrounding large sinus vessels. PLCdelta1 and PLCdelta2 had quite distinct distributions, with the former selectively localized to an endothelial cell population surrounding the chromaffin cells. This observation was supported by experiments on isolated bovine adrenal medullary cells where PLCdelta1 expression was lost when the cell preparation was enriched for chromaffin cells. Antibodies to PLCdelta2 labelled a network of nerve fibres throughout the medulla and clusters of ganglion cells located primarily at the medullary-cortical boundary. PLCdelta2 immunoreactivity was also present in nerve fibres within the adrenal capsule where it appeared to be co-localized with PLCbeta4 staining. © 2005 Elsevier Ireland Ltd. All rights reserved.

Paralemmin-1 is a phosphoprotein, lipid-anchored to the cytoplasmic face of membranes and implicated in plasma membrane dynamics and cell process formation. We report an immunoperoxidase histochemical analysis of the cellular and subcellular localization of paralemmin-1 in the rat tissues where its expression is highest: the brain, the adrenal gland and the kidney. Paralemmin-1 is detected throughout the brain, in neuronal perikarya, axons and dendrites including dendritic spines and also in glial processes. In the adrenal gland, paralemmin-1 is highly expressed in the medulla. The kidney displays a pattern of differential paralemmin-1 expression in various structures and cell types, with high concentrations in cells of the parietal epithelium of Bowman’s capsule, intermediate tubules, distal tubules and principal cells of outer medullary collecting ducts. Mosaics of paralemmin-positive and paralemmin-negative cells are observed in proximal tubules, the parietal epithelium of Bowman’s capsule and the endothelium of many blood vessels. Plasma membrane association in epithelia is often polarized: paralemmin-1 concentrates at the apical membranes of adrenal chromaffin cells, but at the basolateral plasma membranes of proximal and distal tubule cells in the kidney. Paralemmin-1 immunoreactivity exhibits a spotted pattern and can be seen both at plasma membranes and within the cytoplasm, where it is often associated with endomembranes. This discontinuous distribution and the detergent extraction properties of paralemmin-1 suggest an association with lipid microdomains. The findings are consistent with a role for paralemmin-1 in the formation and stabilization of plasma membrane elaborations, in neurons as well as in other cell types.

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the K D of Ca 2 + - dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis.

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the K D of Ca 2 + - dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis.

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the K D of Ca 2 + - dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis.

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the K D of Ca 2 + - dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis.

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2 +_ sensor for fast neurosecretion by analyzing the intracellular Ca 2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the K D of Ca 2 + - dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca 2 + -threshold for secretion due to a twofold increase in the apparent K D of the Ca 2 + sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca 2 + -dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca 2 + dependence of exocytosis.