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Nobuyuki Yanagihara - One of the best experts on this subject based on the ideXlab platform.
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stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin
Journal of Neurochemistry, 2008Co-Authors: Kensuke Utsunomiya, Tat Beng Cheah, Susumu Ueno, Yumiko Toyohira, Nobuyuki Yanagihara, Eiichi Tachikawa, Koji Kajiwara, Futoshi IzumiAbstract:Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on catecholamine synthesis in the cells. Incubating cells with leptin (10 nm) for 20 min increased the synthesis of 14C-Catecholamines from [14C]tyrosine, but not from l-3,4-dihydroxyphenyl [3–14C]alanine. The stimulation of catecholamine synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the synthesis of 14C-Catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-catecholamine synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates catecholamine synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.
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dual effects of daidzein a soy isoflavone on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells
Endocrinology, 2007Co-Authors: Nobuyuki Yanagihara, Susume Ueno, Yumiko Toyohira, Masato Tsutsui, Yuko ShinoharaAbstract:We recently demonstrated the occurrence and functional roles of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of daidzein, a phytoestrogen of soybeans, on catecholamine synthesis and secretion in the cells. Incubation of cells with daidzein for 20 min increased the synthesis of 14C-Catecholamines from [14C]tyrosine but not [14C]dihydroxyphenylalanine, in a concentration-dependent manner (10–1000 nm). The stimulatory effect of daidzein on 14C-catecholamine synthesis was not inhibited by ICI182,780, a classical estrogen receptor inhibitor. Acetylcholine, a physiological secretagogue, stimulated the synthesis of 14C-Catecholamines, which was suppressed by daidzein at 1 μm. Daidzein at high concentrations (1–100 μm) suppressed catecholamine secretion induced by acetylcholine. Furthermore, daidzein (10–1000 nm) inhibited the specific binding of [3H]17β-estradiol to plasma membranes isolated from bovine adrenal medulla. The present findings suggest tha...
Yuko Shinohara - One of the best experts on this subject based on the ideXlab platform.
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dual effects of daidzein a soy isoflavone on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells
Endocrinology, 2007Co-Authors: Nobuyuki Yanagihara, Susume Ueno, Yumiko Toyohira, Masato Tsutsui, Yuko ShinoharaAbstract:We recently demonstrated the occurrence and functional roles of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of daidzein, a phytoestrogen of soybeans, on catecholamine synthesis and secretion in the cells. Incubation of cells with daidzein for 20 min increased the synthesis of 14C-Catecholamines from [14C]tyrosine but not [14C]dihydroxyphenylalanine, in a concentration-dependent manner (10–1000 nm). The stimulatory effect of daidzein on 14C-catecholamine synthesis was not inhibited by ICI182,780, a classical estrogen receptor inhibitor. Acetylcholine, a physiological secretagogue, stimulated the synthesis of 14C-Catecholamines, which was suppressed by daidzein at 1 μm. Daidzein at high concentrations (1–100 μm) suppressed catecholamine secretion induced by acetylcholine. Furthermore, daidzein (10–1000 nm) inhibited the specific binding of [3H]17β-estradiol to plasma membranes isolated from bovine adrenal medulla. The present findings suggest tha...
Sushil K Mahata - One of the best experts on this subject based on the ideXlab platform.
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effect of heart failure on catecholamine granule morphology and storage in chromaffin cells
Journal of Endocrinology, 2016Co-Authors: Sushil K Mahata, Hong Zheng, Kaushik P PatelAbstract:One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated Catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic–adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of Catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased Catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition.
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Chromogranin B: intra- and extra-cellular mechanisms to regulate catecholamine storage and release, in catecholaminergic cells and organisms.
Journal of neurochemistry, 2013Co-Authors: Kuixing Zhang, Manjula Mahata, Jiaur R Gayen, Nilima Biswas, Jose Pablo Miramontes-gonzalez, C. Makena Hightower, Maja Mustapic, Chun-teng Huang, Vivian Hook, Sushil K MahataAbstract:Chromogranin B (CHGB) is the major matrix protein in human catecholamine storage vesicles. CHGB genetic variation alters catecholamine secretion and blood pressure. Here, effective Chgb protein under-expression was achieved by siRNA in PC12 cells, resulting in ~ 48% fewer secretory granules on electron microscopy, diminished capacity for catecholamine uptake (by ~ 79%), and a ~ 73% decline in stores available for nicotinic cholinergic-stimulated secretion. In vivo, loss of Chgb in knockout mice resulted in a ~ 35% decline in chromaffin granule abundance and ~ 44% decline in granule diameter, accompanied by unregulated catecholamine release into plasma. Over-expression of CHGB was achieved by transduction of a CHGB-expressing lentivirus, resulting in ~ 127% elevation in CHGB protein, with ~ 122% greater abundance of secretory granules, but only ~ 14% increased uptake of Catecholamines, and no effect on nicotinic-triggered secretion. Human CHGB protein and its proteolytic fragments inhibited nicotinic-stimulated catecholamine release by ~ 72%. One conserved-region CHGB peptide inhibited nicotinic-triggered secretion by up to ~ 41%, with partial blockade of cationic signal transduction. We conclude that bi-directional quantitative derangements in CHGB abundance result in profound changes in vesicular storage and release of Catecholamines. When processed and released extra-cellularly, CHGB proteolytic fragments exert a feedback effect to inhibit catecholamine secretion, especially during nicotinic cholinergic stimulation. Here, we show reciprocal actions of Chromogranin B (CHGB) on catecholamine storage (stimulation) and release (inhibition). The figure synthesizes consequences of experimental results. Within chromaffin cells, CHGB participates in assembly of catecholamine secretory vesicles, and governs their secretory capacity under nicotinic stimulation. After cleavage and release into the extracellular space, CHGB [and its peptide hCHGB[60–67](KFEVRLLR)] exerts negative feedback effects to inhibit the secretory response to acetylcholine (ACh).
Graeme Eisenhofer - One of the best experts on this subject based on the ideXlab platform.
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intricacies of the molecular machinery of catecholamine biosynthesis and secretion by chromaffin cells of the normal adrenal medulla and in pheochromocytoma and paraganglioma
Cancers, 2019Co-Authors: Annika M A Berends, Lauren Fishbein, Anouk N A Van Der Horstschrivers, Thera P Links, Graeme Eisenhofer, Jacques W.m. Lenders, Ido P. Kema, Michiel N KerstensAbstract:The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the Catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of Catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of Catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression.
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biochemically silent abdominal paragangliomas in patients with mutations in the succinate dehydrogenase subunit b gene
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Karel Pacak, Henri J L M Timmers, Thanh T Huynh, Mones Abuasab, Maria Tsokos, Maria J Merino, Bora E Baysal, Karen T Adams, Graeme EisenhoferAbstract:Context: Patients with adrenal and extra-adrenal abdominal paraganglioma (PGL) almost invariably have increased plasma and urine concentrations of metanephrines, the O-methylated metabolites of Catecholamines. We report four cases of biochemically silent abdominal PGL, in which metanephrines were normal despite extensive disease. Objective: Our objective was to identify the mechanism underlying the lack of catecholamine hypersecretion and metabolism to metanephrines in biochemically silent PGL. Design: This is a descriptive study. Setting: The study was performed at a referral center. Patients: One index case and three additional patients with large abdominal PGL and metastases but with the lack of evidence of catecholamine production, six patients with metastatic catecholamine-producing PGL and a mutation of the succinate dehydrogenase subunit B (SDHB) gene, and 136 random patients with catecholamine-producing PGL were included in the study. Main Outcome Measures: Plasma, urine, and tumor tissue concentrations of Catecholamines and metabolites were calculated with electron microscopy and tyrosine hydroxylase immunohistochemistry. Results: All four patients with biochemically silent PGL had an underlying SDHB mutation. In the index case, the tumor tissue concentration of Catecholamines (1.8 nmol/g) was less than 0.01% that of the median (20,410 nmol/g) for the 136 patients with catecholamine-producing tumors. Electron microscopy showed the presence of normal secretory granules in all four biochemically silent PGLs. Tyrosine hydroxylase immunoreactivity was negligible in the four biochemically silent PGLs but abundant in catecholamine-producing PGLs. Conclusions: Patients with SDHB mutations may present with biochemically silent abdominal PGLs due to defective catecholamine synthesis resulting from the absence of tyrosine hydroxylase. Screening for tumors in patients with SDHB mutations should not be limited to biochemical tests of catecholamine excess.
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impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter svct2
The FASEB Journal, 2003Co-Authors: Stefan R Bornstein, Mayumi Yoshidahiroi, Sotiria Sotiriou, Mark Levine, Hansgeorg Hartwig, Robert L Nussbaum, Graeme EisenhoferAbstract:Ascorbic acid (vitamin C) is a cofactor required in catecholamine synthesis for conversion of dopamine to norepinephrine by dopamine beta-hydroxylase. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die after birth. We therefore investigated whether these mice might have impaired synthesis of Catecholamines. Levels of Catecholamines in brain were unaffected by SVCT2 deficiency. In heart, the only evidence for impaired dopamine beta-hydroxylase activity was a twofold increase in tissue dopamine. An influence of the deficiency on tissue Catecholamines was most prominent in the adrenals where norepinephrine was decreased by 50% and epinephrine, by 81%. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice showed depletion of catecholamine storage vesicles, increased amounts of rough endoplasmic reticulum, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone indicated additional effects of the deficiency on adrenal cortical function. These data show that deranged catecholamine system function in SVCT2 null mice is largely restricted to the adrenal medulla and cannot account for the lethality in these animals. The data, however, establish a crucial role for ascorbic acid in adrenal chromaffin cell function.
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The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral Catecholamines.
Pharmacology & therapeutics, 2001Co-Authors: Graeme EisenhoferAbstract:Catecholamines are translocated across plasma membranes by transporters that belong to two large families with mainly neuronal or extraneuronal locations. In mammals, neuronal uptake of Catecholamines involves the dopamine transporter (DAT) at dopaminergic neurons and the norepinephrine transporter (NET) at noradrenergic neurons. Extraneuronal uptake of Catecholamines is mediated by organic cation transporters (OCTs), including the classic corticosterone-sensitive extraneuronal monoamine transporter. Catecholamine transporters function as part of uptake and metabolizing systems primarily responsible for inactivation of transmitter released by neurons. Additionally, the neuronal catecholamine transporters, recycle Catecholamines for rerelease, thereby reducing requirements for transmitter synthesis. In a broader sense, catecholamine transporters function as part of integrated systems where catecholamine synthesis, release, uptake, and metabolism are regulated in a coordinated fashion in response to the demands placed on the system. Location is also important to function. Neuronal transporters are essential for rapid termination of the signal in neuronal-effector organ transmission, whereas non-neuronal transporters are more important for limiting the spread of the signal and for clearance of Catecholamines from the bloodstream. Besides their presynaptic locations, NET and DAT are also present at several extraneuronal locations, including syncytiotrophoblasts of the placenta and endothelial cells of the lung (NET), stomach and pancreas (DAT). The extraneuronal monoamine transporter shows a broad tissue distribution, whereas the other two non-neuronal catecholamine transporters (OCT1 and OCT2) are mainly localized to the liver, kidney, and intestine. Altered function of peripheral catecholamine transporters may be involved in disturbances of the autonomic nervous system, such as occurs in congestive heart failure and hypernoradrenergic hypertension. Peripheral catecholamine transporters provide important targets for clinical imaging of sympathetic nerves and diagnostic localization and treatment of neuroendocrine tumors, such as neuroblastomas and pheochromocytomas.
Mark R Wightman - One of the best experts on this subject based on the ideXlab platform.
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catecholamine release and uptake in the mouse prefrontal cortex
Journal of Neurochemistry, 2008Co-Authors: Michelle L Mundorf, Joshua D Joseph, Megan C Austin, Marc G Caron, Mark R WightmanAbstract:Monitoring the release and uptake of Catecholamines from terminals in weakly innervated brain regions is an important step in understanding their importance in normal brain function. To that end, we have labeled brain slices from transgenic mice that synthesize placental alkaline phosphatase (PLAP) on neurons containing tyrosine hydroxylase with antibody-fluorochrome conjugate, PLAP-Cy5. Excitation of the fluorochrome enables catecholamine neurons to be visualized in living tissue. Immunohistochemical fluorescence with antibodies to tyrosine hydroxylase and dopamine beta-hydroxylase revealed that the PLAP labeling was specific to catecholamine neurons. In the prefrontal cortex (PFC), immunohistochemical fluorescence of the PLAP along with staining for dopamine transporter (DAT) and norepinephrine transporter (NET) revealed that all three exhibit remarkable spatial overlap. Fluorescence from the PLAP antibody was used to position carbon-fiber microelectrodes adjacent to catecholamine neurons in the PFC. Following incubation with L-DOPA, catecholamine release and subsequent uptake was measured and the effect of uptake inhibitors examined. Release and uptake in NET and DAT knockout mice were also monitored. Uptake rates in the cingulate and prelimbic cortex are so slow that Catecholamines can exist in the extracellular fluid for sufficient time to travel approximately 100 microm. The results support heterologous uptake of Catecholamines and volume transmission in the PFC of mice.
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simultaneous detection of catecholamine exocytosis and ca2 release from single bovine chromaffin cells using a dual microsensor
Analytical Chemistry, 1998Co-Authors: Quan Xin And, Mark R WightmanAbstract:A dual microsensor with a 5 μm radius was fabricated to detect simultaneously Ca2+ and Catecholamines following their secretion from individual biological cells. Detection of Ca2+ was based on changes in fluorescence as a result of its binding with a surface-attached dye, and Catecholamines were detected by amperometry. The fluorescent dye employed, calcium green-1 dextran, is a selective chelator for Ca2+. It was attached to the tip of a carbon fiber electrode by cross-linking with 5% glutaraldehyde. The dual microsensor has a subsecond response time for both Ca2+ and catecholamine concentration changes. Ca2+ concentrations of 100 nM can be detected, while the detection limit for catecholamine is in the micromolar range. The utility of the dual microsensor was evaluated at the surface of bovine adrenal medullary cells. Release of Catecholamines by exocytosis was evoked by transient application of histamine. This was detected by amperometry, and it was found to be accompanied by Ca2+ release, as measured ...
