Effects of Fluoranthene, a Polycyclic Aromatic Hydrocarbon, on cAMP-Dependent Anion Secretion in Human Airway Epithelia

Ito, Yasushi; Son, Masami; Sato, Shinji; Ohashi, Taiki; Kondo, Masashi; Shimokata, Kaoru; Kumakura, Hiroaki

doi:10.1124/jpet.103.059089

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…Similarly, the diol-epoxide metabolites of B(a)P have been found to increase the cytosolic Ca2 + in airway epithelial cells (Jyonouchi et al, 2001). Also, Ito et al (2004) reported that the PAH compound fluoranthene potentates cAMP-dependent anion secretion in airway epithelial cells, thus regulating the membrane potential of these cells.…”

Section: Discussionmentioning

confidence: 94%

Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene

et al. 2007

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The focus of this study was to characterize the impact of gestational exposure to benzo(a)pyrene, [B (a)P] on modulation of glutamate receptor subunit expression that is critical for the maintenance of synaptic plasticity mechanisms during hippocampal or cortical development in offspring. Previous studies have demonstrated that hippocampal and/or cortical synaptic plasticity (as measured by longterm potentiation and S1-cortex spontaneous/evoked neuronal activity) and learning behavior (as measured by fixed-ratio performance operant testing) is significantly impaired in polycyclic aromatic or halogenated aromatic hydrocarbon-exposed offspring as compared to controls. These previous studies have also revealed that brain to body weight ratios are greater in exposed offspring relative to controls indicative of intrauterine growth retardation which has been shown to manifest as low birth weight in offspring. Recent epidemiological studies have identified an effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 Years of life among inner-city children (Perera et al., 2006). The present study utilizes a well-characterized animal model to test the hypothesis that gestational exposure to B(a)P causes dysregulation of developmental ionotropic glutamate receptor subunit expression, namely the N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR) both critical to the expression of synaptic plasticity mechanisms. To mechanistically ascertain the basis of B(a)P-induced plasticity perturbations, timed pregnant Long-Evans rats were exposed in an oral subacute exposure regimen to 0, 25 and 150µg/kg BW B(a)P on gestation days 14-17. The first sub-hypothesis tested whether gestational exposure to B(a)P would result in significant disposition in offspring. The second sub-hypothesis tested whether gestational exposure to B(a)P would result in downregulation of early developmental expression of NMDA and AMPA receptor subunits in the *Corresponding author: Darryl B. Hood, Ph.D., Department of Neurobiology and Neurotoxicology, Center for Molecular and Behavioral Neuroscience, Meharry Medical College, Nashville, TN 37208, USA. Phone (615) 327-6358, FAX: (615) 327-6632. email: dhood@mmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. hippocampus of offspring as well as in primary neuronal cultures. The results of these studies revealed significant: 1) disposition to the hippocampus and cortex, 2) down-regulation of developmental glutamate receptor mRNA and protein subunit expres...

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Section: Discussionmentioning

confidence: 94%

Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene

et al. 2007

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“…This event requires not only the activity of the apical anion channel but also basolateral transporters (Devor et al, 1999;Ito et al, 2004b). The apical CFTR, which is well accepted as a common pathway for HCO 3 Ϫ and Cl Ϫ export (Devor et al, 1999), displays no less than Ϸ60% of maximum conductance at rest, so that the Calu-3 cell is fully capable of anion secretion even under the cAMP-unstimulated state (Moon et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies (Devor et al, 1999;Ito et al, 2004b) reported that the switch between HCO 3 Ϫ secretion and Cl Ϫ secretion is determined by the basolateral membrane potential regulated by a ChTx-sensitive Ca 2ϩ -activated K ϩ channel, KCNN4. Namely, when the basolateral membrane is hyperpolarized by KCNN4 activation, the driving force for HCO 3 Ϫ entry via NBC1 (the Na ϩ -2HCO 3 Ϫ transporter), which carries electrogenically negative charges into the cell, is reduced, whereas the driving force for Cl Ϫ entry across the electroneutral NKCC1 (the Na ϩ -K ϩ -2Cl Ϫ cotransporter) is up-regulated.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical Effects of Hydrogen Peroxide on Human Airway Anion Secretion

Ohashi

Ito²,

Matsuno³

et al. 2006

J Pharmacol Exp Ther

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The present study concerns intriguing effects of hydrogen peroxide (H 2 O 2 ) on cAMP-mediated anion secretion in polarized human airway epithelia. Although H 2 O 2 applied to the apical and basolateral membrane increases short-circuit currents (I SC ) with analogous properties, it has opposite effects on subsequent cAMP-activated I SC responses. Namely, forskolin (FK)-induced I SC responses were down-regulated by the apical presence of H 2 O 2 , whereas they were up-regulated by its basolateral presence. Despite this contrasting effect, oxidative stimuli from either aspect of the monolayer hindered FK-induced increments in cytosolic cAMP levels and apical membrane Cl Ϫ conductance. The site-dependent effects of H 2 O 2 were reproduced in the responses to 8-bromo-cAMP. Estimation of the anionic composition of the I SC revealed that the FK up-regulated both bumetanide [an Na Ϫ secretion by an increase in Cl Ϫ uptake via basolateral NKCC1, whose sensitivities to cAMP/protein kinase A are up-regulated, overcoming the H 2 O 2 -induced inhibition of cAMP-mediated apical anion conductance. The basolateral membrane-specific effects of H 2 O 2 may be relevant to the basolateral cytoskeleton, which is believed to interact with NKCC1.

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“…The purpose of the present study is to examine and compare the effects of Cordyceps extracts on the ion transport in Calu-3 airway epithelial cell monolayer model system. By using short-circuit current (Isc) measurement, the effects of certain secretagogues on transepithelial ion transport could be demonstrated (Cobb et al, 2003;Ito et al, 2004). Since the chemical markers for Cordyceps sinensis and Cordyceps militaris, adenosine and cordycepin, respectively, have been found to vary in amount between the different parts of fruiting bodies (Shiao et al, 1994;Li et al, 2001b;Chinese Pharmacopoeia Commission, 2005), the efficacies of the extracts from stroma (S) and larva (L)/pupa (P), were also compared in the present study.…”

Section: Introductionmentioning

confidence: 99%

Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells

Yue

Lau

Fung

et al. 2008

Journal of Ethnopharmacology

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Effects of Fluoranthene, a Polycyclic Aromatic Hydrocarbon, on cAMP-Dependent Anion Secretion in Human Airway Epithelia

Cited by 12 publications

References 37 publications

Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene

Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene

Paradoxical Effects of Hydrogen Peroxide on Human Airway Anion Secretion

Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells

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