scholarly journals Reduced Activation of the Synaptic-Type GABAA Receptor Following Prolonged Exposure to Low Concentrations of Agonists: Relationship between Tonic Activity and Desensitization

2020 ◽  
Vol 98 (6) ◽  
pp. 762-769
Author(s):  
Spencer R. Pierce ◽  
Allison L. Germann ◽  
Alex S. Evers ◽  
Joe Henry Steinbach ◽  
Gustav Akk
Keyword(s):  
Gabaa Receptor ◽  
Prolonged Exposure ◽  
Tonic Activity ◽  
Low Concentrations

scholarly journals Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 606
Author(s):  
Claudia Meindl ◽  
Kristin Öhlinger ◽  
Verena Zrim ◽  
Thomas Steinkogler ◽  
Eleonore Fröhlich
Keyword(s):  
Prolonged Exposure ◽  
A549 Cells ◽  
Cytokine Release ◽  
Transient Effects ◽  
Particle Uptake ◽  
Particle Accumulation ◽  
Low Concentrations ◽  
Culture Models ◽  
20 Nm ◽  
Inhaled Nanoparticles

Respiratory exposure of humans to environmental and therapeutic nanoparticles repeatedly occurs at relatively low concentrations. To identify adverse effects of particle accumulation under realistic conditions, monocultures of Calu-3 and A549 cells and co-cultures of A549 and THP-1 macrophages in the air–liquid interphase culture were exposed repeatedly to 2 µg/cm2 20 nm and 200 nm polystyrene particles with different functionalization. Particle accumulation, transepithelial electrical resistance, dextran (3–70 kDa) uptake and proinflammatory cytokine secretion were determined over 28 days. Calu-3 cells showed constant particle uptake without any change in barrier function and cytokine release. A549 cells preferentially ingested amino- and not-functionalized particles combined with decreased endocytosis. Cytokine release was transiently increased upon exposure to all particles. Carboxyl-functionalized demonstrated higher uptake and higher cytokine release than the other particles in the A549/THP-1 co-cultures. The evaluated respiratory cells and co-cultures ingested different amounts and types of particles and caused small (partly transient) effects. The data suggest that the healthy cells can adapt to low doses of non-cytotoxic particles.

Features of the composition of red blood in persons working with pesticides in greenhouses

1985 ◽  
Vol 66 (1) ◽  
pp. 60-63
Author(s):  
A. V. Romash
Keyword(s):  
Prolonged Exposure ◽  
Low Concentrations

There are indications in the literature that prolonged exposure to low concentrations of many chemicals can lead to the development of anemia [2, 7, 8].

Prolonged exposure to hypobaric hypoxia transiently reduces GABAA receptor number in mice cerebral cortex

2001 ◽  
Vol 894 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Mariano Sebastián Viapiano ◽  
Alba Marta Mitridate de Novara ◽  
Sara Fiszer de Plazas ◽  
Carlos Eduardo Bozzini
Keyword(s):  
Cerebral Cortex ◽  
Gabaa Receptor ◽  
Hypobaric Hypoxia ◽  
Prolonged Exposure ◽  
Receptor Number

Oxidants and regulation of K+-Cl−cotransport in equine red blood cells

2000 ◽  
Vol 279 (4) ◽  
pp. C981-C989 ◽  
Author(s):  
M. C. Muzyamba ◽  
P. F. Speake ◽  
J. S. Gibson
Keyword(s):  
Carbon Monoxide ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Prolonged Exposure ◽  
Reduced Glutathione ◽  
Low Concentrations ◽  
High Concentrations

The effect of oxidants on K+-Cl−cotransport (KCC) was investigated in equine red blood cells. Carbon monoxide mimicked O2. The substituted benzaldehyde, 12C79 (5 mM), markedly increased O2affinity. In N2, however, O2saturation was low (<10%) but KCC remained active. Nitrite (NO2−) oxidized heme to methemoglobin (metHb). High concentrations of NO2−(1 and 5 mM vs. 0.5 mM) increased KCC activity above control levels; it became O2independent but remained sensitive to other stimuli. 1-Chloro-2,4-dinitrobenzene (1–3 mM) depleted reduced glutathione (GSH). Prolonged exposure (60–120 min, 1 mM) or high concentrations (3 mM) stimulated an O2-independent KCC activity; short exposures and low concentrations (30 min, 0.5 or 1 mM) did not. The effect of these manipulations was correlated with changes in GSH and metHb concentrations. An oxy conformation of Hb was necessary for KCC activation. An increase in its activity over the level found in oxygenated control cells required both accumulation of metHb and depletion of GSH. Findings are relevant to understanding the physiology and pathology of regulation of KCC.

Mechanisms of H+ injury in rabbit esophageal epithelium

1984 ◽  
Vol 246 (6) ◽  
pp. G718-G724 ◽  
Author(s):  
R. C. Orlando ◽  
J. C. Bryson ◽  
D. W. Powell
Keyword(s):  
Atpase Activity ◽  
Prolonged Exposure ◽  
Cell Volume Regulation ◽  
Initial Increase ◽  
Na Transport ◽  
High Concentration ◽  
Low Concentrations ◽  
Stratified Squamous Epithelium

We previously postulated that active Na transport by the esophageal stratified squamous epithelium is important for maintenance of its barrier function. To investigate this further we studied the effects of HCl on the in vivo esophageal potential difference (PD), on in vitro Na transport, and on esophageal Na-K-ATPase activity. In vivo esophageal perfusion with low concentrations of HCl (20 or 40 mM) increased the PD and a high concentration (120 mM) decreased it. An intermediate concentration (80 mM) caused a biphasic response with an initial increase in PD followed by a progressive decrease in PD. In vitro transport studies were performed to explain the increased in vivo PD. In the presence of luminal H+ the increased PD resulted from H+ diffusion from lumen to blood, whereas after H+ exposure the increased PD was due largely to increased net Na transport from lumen to blood through an amiloride-sensitive mechanism. In tissues with prolonged exposure to 80 mM HCl (PD decreased 80-100%), Na-K-ATPase activity was significantly inhibited (1.94 +/- 0.32 vs. 5.12 +/- 0.73 mumol P X mg prot-1 X h-1). Thus, HCl initially increases the in vivo esophageal PD by H+ transport from lumen to blood, a process replaced by stimulated net Na transport when H+ is replaced by Na. Prolonged acid exposure ultimately decreases Na exit from cells by inhibiting Na-K-ATPase activity. This sequence suggests that alterations in Na transport could result in cell edema and necrosis via loss of cell volume regulation.

The Alkyl Chain Dependence of the Effect of Normal Alcohols on Agonist-induced Nicotinic Acetylcholine Receptor Desensitization Kinetics 

1999 ◽  
Vol 91 (1) ◽  
pp. 222-230 ◽  
Author(s):  
Douglas E. Raines ◽  
Vinu T. Zachariah
Keyword(s):  
Rate Constant ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Prolonged Exposure ◽  
Maximal Rate ◽  
Nicotinic Acetylcholine ◽  
Agonist Affinity ◽  
Low Concentrations ◽  
Agonist Concentration ◽  
Alcohol Effects

Background The nAcChoR is the prototypical member of a superfamily of ligand-gated ion channels that are all relevant targets of anesthetics and undergo desensitization upon prolonged exposure to agonist. This study was designed to investigate the effects of representative normal alcohols on the apparent rate of acetylcholine-induced nAcChoR desensitization. Methods Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana. The apparent rate of acetylcholine-induced desensitization in the presence and absence of normal alcohols was measured using stopped-flow fluorescence. Results Normal alcohols as long as octanol (the longest studied) increased the apparent rate of desensitization induced by low concentrations of acetylcholine, shifting the agonist concentration-response curve for desensitization to the left Ethanol butanol, and, to a lesser extent, hexanol increased the maximal rate of desensitization induced by high, saturating concentrations of agonist. Beyond hexanol, heptanol and octanol had no effect on this maximal apparent rate of desensitization, even at concentrations that approach those that directly induce desensitization in the absence of agonist. Conclusion Normal alcohols ranging from ethanol to octanol increase the apparent affinity of nAcChoR for agonist with potencies that are proportional to their hydrophobicities. However, normal alcohol effects on the rate constant for desensitization show a cutoff beyond hexanoL This suggests that the effects of normal alcohols on the apparent agonist affinity and rate constant for desensitization of nAcChoR may be modulated by distinct sites that have different steric constraints; the site(s) responsible for increasing the maximal rate of desensitization are predicted to be smaller than those that increase the apparent agonist affinity.

Toxicity of cadmium and zinc mixtures to the decaudized cercarial life span of Diplostomum spathaceum

2005 ◽  
Vol 79 (4) ◽  
pp. 353-359 ◽  
Author(s):  
N.J. Morley ◽  
M. Crane ◽  
J.W. Lewis
Keyword(s):  
Life Span ◽  
Prolonged Exposure ◽  
Exposure Period ◽  
Fish Host ◽  
High Dose ◽  
Metal Mixtures ◽  
Diplostomum Spathaceum ◽  
Low Concentrations ◽  
Metal Treatment ◽  
Pre Treatment

AbstractThe effects of cadmium and zinc mixtures at concentrations ranging from 0.1 to 10,000 μg l−1 on the life-span of decaudized cercarial bodies (cercariae that have shed their tails) of Diplostomum spathaceum (Trematoda: Diplostomatidae) was investigated. Cercariae were exposed to metal mixtures of equal and unequal concentrations, and a low-dose pre-treatment followed by a high-dose exposure mixtures. Metal mixtures demonstrated variable effects on decaudized cercariae either by increasing or reducing their life-span compared to single metal exposures dependent on concentration and the type of mixed metal treatment. Prolonged exposure to equal metal mixtures at low concentrations (0.1–100 μg l−1) resulted in a reduction in the life-span of decaudized cercariae at 0.1 and 100 μg l−1 in those individuals decaudized during the initial 24 h exposure period compared with those decaudized during the final 24 h period of cercarial survival, whilst in controls there was no significant life-span change between the two time periods. Decaudized cercariae which were exposed to low concentrations (0.1–100 μg l−1) of equal metal mixtures were also evaluated for their role as an indicator of larval ‘fitness’ for migrating through the tissues of their target fish host for those individuals decaudized during the initial 24 h exposure period, and demonstrated only a limited change in their life-span compared to control and single metal exposures. The importance of metal mixtures in parasite establishment in the fish host is discussed.

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