Ca<sup>2+</sup>‐independent vesicular catecholamine release  in PC12 cells by nanomolar concentrations of Pb<sup>2+</sup>

Westerink, Remco H.S.; Vijverberg, Henk P.M.

doi:10.1046/j.0022-3042.2001.00751.x

Cited by 41 publications

(37 citation statements)

References 46 publications

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“…High K ϩ stimulation evoked vesicular catecholamine release in Ͼ80% of all cells tested, but the frequency of exocytotic events varied considerably between cells. Few very large events were often observed during the first stimulation and some rundown of the number of exocytotic events per stimulus occurred over time, as reported previously (Westerink and Vijverberg, 2002). After cessation of high K ϩ stimulation, the frequency of exocytotic events rapidly declined to a low basal level of 1.2 Ϯ 1.0 min Ϫ1 (n ϭ 10).…”

Section: Acute Effectsmentioning

confidence: 52%

“…1 and 2) are not unique, since PCB 126 has previously been shown to affect neuronal functioning (Kodavanti et al, 1993;Angus and Contreras, 1996;Inglefield et al, 2001). Effects on vesicle contents may not be expected in acute experiments on PC12 cells, since previous studies have shown that vesicle cycling in these cells is slow and the total number of vesicles that can be released from a single PC12 cells in an acute experiment is limited (Westerink et al, 2000;Westerink and Vijverberg, 2002). Establishing a reduction of vesicle contents may require exposure to PCBs for more than 15 min, which was the exposure period in the acute experiments.…”

Section: Discussionmentioning

confidence: 99%

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Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

Westerink

Vijverberg

2002

Toxicology and Applied Pharmacology

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Key Words: PCB; quantal catecholamine release; rat PC12 phaeochromocytoma cells; carbon fiber microelectrode amperometry.The neurotoxic potential of specific polychlorinated biphenyls (PCBs) and related substances, many of which persist in the environment and may accumulate in biological tissues, is a matter of toxicological concern (Tilson and . Behavioral symptoms and brain neurotransmitter levels in exposed animals, as well as in vitro experimental data, indicate involvement of monoaminergic systems in PCB neurotoxicity and of the dopaminergic system in particular (for review see Seegal, 1995).Potential mechanisms underlying the effects of PCBs on the catecholaminergic system have been addressed using in vitro model systems. Several of the ortho-substituted, nonplanar PCB congeners reduce the dopamine contents of rat phaeochromocytoma (PC12) cells after 6 h of exposure with IC50 values Ͻ 100 M, whereas coplanar congeners are inactive in this respect . In an additional study of PC12 cells, the threshold concentrations of several PCB congeners to affect cellular dopamine contents and basal and evoked dopamine release were reported to be close to 10 M (Angus and Contreras, 1996). In primary cultured bovine adrenal chromaffin cells, exposed to 50 -100 M of the nonplanar congener 2,2Ј,4,4Ј-tetrachlorobiphenyl for 1 and 5 days, cellular catecholamine contents and evoked catecholamine release were reduced, and basal catecholamine release was enhanced. The coplanar congener 3,3Ј,4,4Ј-tetrachlorobiphenyl did not cause any of these effects at concentrations up to 100 M (Messeri et al., 1997).Experiments with rat PC12 and mouse neuroblastoma N1E-115 cells have shown that 30 -200 M 2,2Ј-dichlorobiphenyl (PCB 4) inhibits tyrosine hydroxylase. A less potent, partial inhibition of tyrosine hydroxylase activity by PCB 4 was observed in minced rat corpus striatum (Choksi et al., 1997). Uptake of dopamine into rat brain synaptosomes and into rat brain synaptic vesicles are both inhibited by micromolar concentrations of PCBs. Highly chlorinated congeners appear to inhibit the plasma membrane dopamine transporter more potently than the vesicular monoamine transporter (Mariussen et al., 1999;Mariussen and Fonnum, 2001). Exposure of primary cultured rat neocortical and cerebellar granule cells to micromolar concentrations of PCBs may lead to variety of early transient, sustained, and oscillatory elevations of the intracellular Ca 2ϩ concentration (Kodavanti et al., 1993;Carpenter et al., 1997;Mundy et al., 1999;Inglefield and Shafer, 2000;Inglefield et al., 2001). Elevation of the intracellular Ca 2ϩ concentration and of Ca 2ϩ /calmodulin-dependent protein kinase II (CaM kinase II) activation, i.e., common intracellular signaling pathways, appear to be involved in PCB-induced release of insulin from RINm5F rat insuloma cells (Fischer et al., 1996(Fischer et al., , 1999 to cause an elevation of the intracellular Ca 2ϩ concentration (Wong et al., 2001). Several of the alleged mechanisms of action of PCBs would be expected to lead t...

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Section: Acute Effectsmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

Westerink

Vijverberg

2002

Toxicology and Applied Pharmacology

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“…These cells can be differentiated into neuron-like cells and produce catecholamines as adrenalin, noradrenalin and dopamine like their organ counterpart, the chromaffin cells from the adrenal gland. Chromaffin cells and PC12 cells have been widely used for pharmacological and toxicological investigations of heavy metals (Weinsberg et al, 1995;Westerink and Vijverberg, 2002a), polychlorinated biphenyls (Messeri et al, 1997;Westerink and Vijverberg, 2002b) and alkaloids (Lee and Kim, 1996;Gafni et al, 1997;Bickmeyer et al, 1998;Kim et al, 2001;Smith et al, 2002). Hormone secretion is triggered by influx of extracellular calcium through voltage dependent calcium channels, which can be monitored using calcium sensitive dyes (Grynkiewicz et al, 1985;Deitmer and Schild, 2000).…”

Section: Introductionmentioning

confidence: 99%

A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

Bickmeyer¹,

Assmann²,

Köck³

et al. 2005

Environmental Toxicology and Pharmacology

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A secondary metabolite from sponges of the genus Agelas, 4,5-dibromopyrrole-2-carboxylic acid, which is well known as feeding deterrent, was investigated for effects on the cellular calcium homeostasis in PC12 cells. 4,5-Dibromopyrrole-2-carboxylic acid did not change intracellular calcium levels if applied alone without cell depolarization. During depolarization of the cellular membrane using high potassium solution, a dose dependent reduction of intracellular calcium elevation was revealed utilizing Fura II as calcium indicator. Significant reduction was seen at concentrations higher than 30 M in a series of experiments, but in single experiments a concentration of 300 nM was still reversible effective. In the same concentration range, the onset of depolarization induced calcium elevations was significantly delayed by 4,5-dibromopyrrole-2-carboxylic acid. Dose dependent reduction and delay of depolarization evoked calcium elevations are probably due to a reduction of calcium entry via voltage operated calcium channels. One cellular mode of action of the feeding deterrent potential of 4,5-dibromopyrrole-2-carboxylic acid to fishes may be an interaction with the cellular calcium homeostasis of exposed cells.

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“…Corticosterone, an important stress hormone, regulates dopaminergic neurotransmission at the level of DA D-1 receptors and DA synthesis [271,272]. Chronic exposure to the synthetic glucocorticoid dexamethasone, which induces a chromaffin cell-like phenotype in neuroendocrine PC12 cells, was shown to increase the activity of TH, the amount of stored catecholamines, the Ca 2+ current magnitude, the frequency of depolarization-induced catecholamine exocytosis, and the amount of catecholamines released per fusion event [206,273,274]. In line with this, corticosterone increases extracellular [DA] and locomotor activity, whereas suppression of endogenous glucocorticoid secretion decreases basal and depolarization-induced DA release in the NAcc as well as apomorphine-induced locomotor activity [275].…”

Section: Endogenous and Exogenous Factors Modulating Catecholamine/damentioning

confidence: 99%

Targeting Exocytosis: Ins and Outs of the Modulation of Quantal Dopamine Release

Westerink

2006

CNSNDDT

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Dopaminergic neurotransmission is mediated by the vesicular release of dopamine (DA), i.e. DA exocytosis. DA exocytosis and its modulation are generally believed to affect neuronal communication, development, maintenance and survival, and contribute to extracellular DA levels in the brain. As a result, DA exocytosis likely plays an important role in several neurological and psychiatric disorders, like Parkinson's disease (PD) and schizophrenia. As exocytosis is part of a sophisticated ensemble of processes, it can be modulated at different levels, including DA synthesis, uptake and vesicular transport as well as Ca 2+ -homeostasis and exocytotic proteins. Nonetheless, to be effective, modulation of exocytosis should result in functional changes, which are reflected by changes in release frequency, vesicle contents, and the time course of the exocytotic event. As will be shown in this review, functional changes in DA exocytosis can be produced by e.g. pharmacological/drug treatment, feedback mechanisms and up/down-regulation of exocytosis-related proteins. Moreover, the mode of DA exocytosis, i.e. classical full fusion or kiss-and-run exocytosis, could also serve as a potential target for functional modulation of dopaminergic neurotransmission. Since the onset and progression of neurological and psychiatric disorders often show a strong correlation with changes in brain DA levels, DA synthesis, transport or uptake, the findings described in this review highlight the importance of the modulation of (the mode of) DA exocytosis for normal progression of dopaminergic neurotransmission and the potential of exocytotic processes as drug targets.

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Ca²⁺‐independent vesicular catecholamine release in PC12 cells by nanomolar concentrations of Pb²⁺

Cited by 41 publications

References 46 publications

Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

Targeting Exocytosis: Ins and Outs of the Modulation of Quantal Dopamine Release

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Ca2+‐independent vesicular catecholamine release in PC12 cells by nanomolar concentrations of Pb2+

Cited by 41 publications

References 46 publications

Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

Targeting Exocytosis: Ins and Outs of the Modulation of Quantal Dopamine Release

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Product

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Ca²⁺‐independent vesicular catecholamine release in PC12 cells by nanomolar concentrations of Pb²⁺