Exposure to organic solvents may cause narcotic effects. At the cellular level, these narcotic effects have been associated with a reduction in neuronal excitability caused by changes in membrane structure and function. In order to critically test whether changes in membrane geometry contribute to these narcotic effects, cultured human SH-SY5Y neuroblastoma cells have been exposed to selected organic solvents.
View Article and Find Full Text PDFIt is generally acknowledged that Pb(2+), which is sequestered by live cells from their direct environment, affects a large number of cellular processes at picomolar to micromolar concentrations. However, resolving the specific molecular targets and mechanisms responsible for the neurotoxic effects of this xenobiotic metal is hampered by the lack of suitable tools to investigate the intracellular dynamics of Pb(2+) at low concentrations. Fluorescent Ca(2+) indicators have been used as Pb(2+) sensors and have proven useful to detect cellular Pb(2+) entry and to estimate the overall intracellular free Pb(2+) concentration associated with adverse cellular effects.
View Article and Find Full Text PDFEthylbenzene and para-xylene (p-xylene), but not the chemically closely related organic solvents ortho-xylene (o-xylene) and meta-xylene (m-xylene), are known to cause ototoxicity and irreversible hearing loss, though the underlying mechanisms are still unknown. In this study, effects of ethylbenzene and of p-, o-, and m-xylene on human heteromeric alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated using the two-electrode voltage clamp technique. ACh dose-dependently evoked an alpha9alpha10 nAChR-mediated ion current with an EC(50) of 137 microM.
View Article and Find Full Text PDFBackground: Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants.
Objective: Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells.
Methods: We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively.
Background: Increasing environmental levels of brominated flame retardants raise concern about possible adverse effects, particularly through early developmental exposure.
Objective: The objective of this research was to investigate neurodevelopmental mechanisms underlying previously observed behavioral impairments observed after neonatal exposure to polybrominated diphenyl ethers (PBDEs).
Methods: C57Bl/6 mice received a single oral dose of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on postnatal day (PND) 10 (i.
Effects of cholinergic drugs on human alpha4beta2 nicotinic acetylcholine receptors expressed in Xenopus oocytes have been investigated in electrophysiological and ligand binding experiments. Atropine, scopolamine, physostigmine, and tacrine combine potentiation of ion current induced by low concentrations of acetylcholine with inhibition of ion current evoked by high concentrations of acetylcholine. Rivastigmine, galanthamine, and dichlorvos cause only inhibition of ion current evoked by low concentrations of acetylcholine.
View Article and Find Full Text PDFChronic and acute exposure to organophosphate (OP) pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. It is suggested that other brain proteins are involved. Effects of commonly used organophosphate pesticides on rat neuronal alpha4beta2 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique.
View Article and Find Full Text PDFThe mechanism by which carbamate pesticides inhibit rat alpha4beta2 nicotinic acetylcholine (ACh) receptors (nAChRs) expressed in Xenopus laevis oocytes has been investigated using the two-electrode voltage clamp technique. Carbaryl, S-ethyl N,N-dipropylthiocarbamate (EPTC), and fenoxycarb inhibit ACh-induced ion currents in a concentration-dependent way. EPTC and fenoxycarb inhibit ion currents induced by 1 mM ACh with 3-fold to 5-fold higher potency than ion currents induced by 1 microM ACh.
View Article and Find Full Text PDFEffects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency order of six carbamates to inhibit alpha4beta4 nicotinic receptors is fenoxycarb > EPTC > carbaryl, bendiocarb > propoxur > aldicarb with IC50 values ranging from 3 microM for fenoxycarb to 165 microM for propoxur and >1 mM for aldicarb.
View Article and Find Full Text PDFPartition coefficients of 28 volatile organic solvents (13 alkylbenzenes, 10 chlorinated hydrocarbons, and 5 ketones) in olive oil, saline, and rat brain tissue homogenates were measured by equilibration in a closed vial and subsequent gas-chromatographic analysis of headspace air. The values of oil and saline partition coefficients correlate well with previously reported data. Brain partition coefficients were fit to a bilinear equation of the form P(brain:air) = alpha(o)P(oil:air) + alpha(s)P(saline:air) + c.
View Article and Find Full Text PDFEffects of the neurotoxic organic solvent toluene on human neuronal nicotinic acetylcholine (nACh) and gamma-aminobutyric acid type A (GABA(A)) neurotransmitter receptors were investigated in whole-cell voltage-clamped IMR-32 neuroblastoma cells. Ion currents evoked by near maximum effective concentrations of 1 mM acetylcholine (ACh) and 1 mM gamma-aminobutyric acid (GABA) are inhibited by toluene in a concentration-dependent way. Concentration-effect curves of toluene yield IC(50) values of 276+/-26 and 39+/-6 microM and slope factors of 1.
View Article and Find Full Text PDFSince Pb(2+) substitutes for Ca(2+) in essential steps leading to exocytosis, we have investigated whether Ca(2+) and Pb(2+) induce exocytosis through similar pathways. Vesicular catecholamine release was measured from dexamethasone-differentiated PC12 cells using carbon fiber microelectrode amperometry. Effects of drugs known to modulate PKC (PMA, staurosporine), calcineurin (cyclosporin A), calmodulin (W7), and CaM kinase II (KN-62) activity were investigated in intact and in ionomycin-permeabilized PC12 cells.
View Article and Find Full Text PDFToxicol Appl Pharmacol
September 2002
Effects of selected polychlorinated biphenyls (PCBs) on vesicular catecholamine release from rat PC12 phaeochromocytoma cells have been measured using carbon fiber microelectrode amperometry. Exocytotic responses were evoked by superfusion of single PC12 cells with high K(+) saline. Subsequent exposure of the same cells to saline containing the nonplanar congener 2,2'-dichlorobiphenyl (PCB 4) and the coplanar congener 3,3',4,4',5-pentachlorobiphenyl (PCB 126) at concentrations between 5 and 25 microM for 15 min caused an enhancement of the frequency of basal vesicular catecholamine release at the lower concentrations but not at the high concentrations tested.
View Article and Find Full Text PDFAcute effects of toluene on vesicular catecholamine release from intact PC12 phaeochromocytoma cells have been investigated using carbon fiber microelectrode amperometry. The frequency of vesicles released is low under basal conditions and is enhanced by depolarization. Toluene causes an increase in basal release frequency.
View Article and Find Full Text PDFEffects of Pb(2+) on vesicular catecholamine release in intact and ionomycin-permeabilized PC12 cells were investigated using carbon fibre microelectrode amperometry. Changes in intracellular Pb(2+) and Ca(2+) were measured from indo-1 fluorescence by confocal laser scanning microscopy. Depolarization of intact cells and superfusion of permeabilized cells with saline containing > or = 100 microm Ca(2+) rapidly evokes quantal catecholamine release.
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