Bisphenol A Inhibits Cl<sup>−</sup> Secretion by Inhibition of Basolateral K<sup>+</sup> Conductance in Human Airway Epithelial Cells

Ito, Yasushi; Sato, Shinji; Son, Masami; Kondo, Masashi; Kumakura, Hiroaki; Takagi, Kenzo; Yamaki, Kenichi

doi:10.1124/jpet.302.1.80

Cited by 14 publications

(7 citation statements)

References 38 publications

(51 reference statements)

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“…For this measurement, the basolateral membrane was permeabilized with the pore-forming antibiotic nystatin (100 M) for more than 30 min. This procedure avoids the complexities associated with basolateral ion transporters and permits analyses of apical membrane Cl Ϫ conductance (12,15). Complete permeabilization of the basolateral membrane with 100 M nystatin was preliminarily confirmed by basolateral application of bumetanide, an inhibitor of the Na ϩ -K ϩ -2Cl Ϫ cotransporter located on the basolateral membrane of Calu-3 cells, and a bumetanide-sensitive component was not detected 30 min after addition of nystatin (data not shown).…”

Section: Measurement Of Apical CL ϫ Current and Basolateral K ؉ Currentmentioning

confidence: 88%

“…In this basolateral solution, CaCl 2 was increased to 4 mM to compensate for the Ca 2ϩ -chelating capacity of the gluconate (17). On the other hand, the K ϩ current across the basolateral membrane (I K ) was estimated after permeabilization of the apical membrane with nystatin (50 M) for more than 30 min and establishment of an apical-to-basolateral K ϩ concentration gradient (12,15). Complete permeabilization of the apical membrane with 50 M nystatin had been confirmed by apical application of phlorizin, an inhibitor of the Na ϩ -glucose transporter located on the apical membrane of this cell line (18).…”

Section: Measurement Of Apical CL ϫ Current and Basolateral K ؉ Currentmentioning

confidence: 99%

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Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Son

Ito²,

Sato³

et al. 2004

Am J Respir Cell Mol Biol

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The present study investigated mechanisms underlying apical and basolateral P2Y(1)-mediated Cl(-) secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (I(sc)) with different properties via P2Y(1) receptors. The former comprised an immediate rise followed by a slow attenuation, whereas the latter was a transient rise with a higher peak and shorter duration (< 2 min). The actions of ATP were simulated by those of ADP, ADPbetaS, and ATPgammaS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH(3)) were without any effect on the bilateral ATP-induced I(sc), which were, in contrast, attenuated by a phosphatidylcholine-phospholipase C inhibitor (D609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Ca(2+) chelator, 1,2-bis (o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, or a Ca(2+)-activated K(+) channel inhibitor, charybdotoxin, although differential Ca(2+) signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the I(sc) and the basolateral K(+) current rather than the apical Cl(-) current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y(1) receptors couple with both phosphatidylcholine-phospholipase C and adenylate cyclase, leading to Cl(-) secretion, whose rate is essentially regulated by the Ca(2+)-activated K(+) channel-mediated K(+) conductance. This suggests the importance of this channel in airway mucociliary clearance.

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Section: Measurement Of Apical CL ϫ Current and Basolateral K ؉ Currentmentioning

confidence: 88%

Section: Measurement Of Apical CL ϫ Current and Basolateral K ؉ Currentmentioning

confidence: 99%

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Son

Ito²,

Sato³

et al. 2004

Am J Respir Cell Mol Biol

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“…To investigate apical membrane Cl 2 conductance, apical membrane Cl 2 currents (aI Cl ) in the apical-to-basolateral Cl 2 concentration gradient were estimated after permeabilization of the basolateral membrane with nystatin (100 mM) for more than 20 minutes, as previously described (17)(18)(19). The aI Cl reflects Cl 2 permeability through CFTR in Calu-3 cells (18,20).…”

Section: Bioelectric Measurementsmentioning

confidence: 99%

Capsaicinoids Regulate Airway Anion Transporters through Rho Kinase– and Cyclic AMP–Dependent Mechanisms

Hibino

Morise

Ito

et al. 2011

Am J Respir Cell Mol Biol

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To investigate the effects of capsaicinoids on airway anion transporters, we recorded and analyzed transepithelial currents in human airway epithelial Calu-3 cells. Application of capsaicin (100 μM) attenuated vectorial anion transport, estimated as short-circuit currents (I(SC)), before and after stimulation by forskolin (10 μM) with concomitant reduction of cytosolic cyclic AMP (cAMP) levels. The capsaicin-induced inhibition of I(SC) was also observed in the response to 8-bromo-cAMP (1 mM, a cell-permeable cAMP analog) and 3-isobutyl-1-methylxanthine (1 mM, an inhibitor of phosphodiesterases). The capsaicin-induced inhibition of I(SC) was attributed to suppression of bumetanide (an inhibitor of the basolateral Na(+)-K(+)-2 Cl(-) cotransporter 1)- and 4,4'-dinitrostilbene-2,2'-disulfonic acid (an inhibitor of basolateral HCO(3)(-)-dependent anion transporters)-sensitive components, which reflect anion uptake via basolateral cAMP-dependent anion transporters. In contrast, capsaicin potentiated apical Cl(-) conductance, which reflects conductivity through the cystic fibrosis transmembrane conductance regulator, a cAMP-regulated Cl(-) channel. All these paradoxical effects of capsaicin were mimicked by capsazepine. Forskolin application also increased phosphorylated myosin phosphatase target subunit 1, and the phosphorylation was prevented by capsaicin and capsazepine, suggesting that these capsaicinoids assume aspects of Rho kinase inhibitors. We also found that the increments in apical Cl(-) conductance were caused by conventional Rho kinase inhibitors, Y-27632 (20 μM) and HA-1077 (20 μM), with selective inhibition of basolateral Na(+)-K(+)-2 Cl(-) cotransporter 1. Collectively, capsaicinoids inhibit cAMP-mediated anion transport through down-regulation of basolateral anion uptake, paradoxically accompanied by up-regulation of apical cystic fibrosis transmembrane conductance regulator-mediated anion conductance. The latter is mediated by inhibition of Rho-kinase, which is believed to interact with actin cytoskeleton.

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“…Similarly, we found that CPZ attenuated adenosine or NECA-induced I sc by ϳ30% (data not shown). However, CPZ also blocks various membrane receptors and ion channels and reportedly inhibits basolateral K Ca channels in Calu-3 cells (21). This direct effect on basolateral K Ca channels, also observed by us in Ussing chamber and singlechannel studies (data not shown), compromises the utility of CPZ as a tool for determining whether adenosine activates potassium channels by PLA2 signaling.…”

Section: Might Adenosine Activate Other Basolateral Potassium Channels?mentioning

confidence: 71%

“…Clotrimazole (20 M), a commonly used blocker of K Ca channels (10,13,21,46), reduced the ⌬I sc induced by 10 M mucosal adenosine by ϳ47% (Fig. 2, A and B).…”

Section: Adenosine-induced I Sc Was Dependent On Neither Pkc Nor Crosmentioning

confidence: 97%

Apical adenosine regulates basolateral Ca²⁺-activated potassium channels in human airway Calu-3 epithelial cells

Wang

Sun²,

Zhang³

et al. 2008

American Journal of Physiology-Cell Physiology

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Bisphenol A Inhibits Cl⁻ Secretion by Inhibition of Basolateral K⁺ Conductance in Human Airway Epithelial Cells

Cited by 14 publications

References 38 publications

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Capsaicinoids Regulate Airway Anion Transporters through Rho Kinase– and Cyclic AMP–Dependent Mechanisms

Apical adenosine regulates basolateral Ca²⁺-activated potassium channels in human airway Calu-3 epithelial cells

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Bisphenol A Inhibits Cl− Secretion by Inhibition of Basolateral K+ Conductance in Human Airway Epithelial Cells

Cited by 14 publications

References 38 publications

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

Capsaicinoids Regulate Airway Anion Transporters through Rho Kinase– and Cyclic AMP–Dependent Mechanisms

Apical adenosine regulates basolateral Ca2+-activated potassium channels in human airway Calu-3 epithelial cells

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Bisphenol A Inhibits Cl⁻ Secretion by Inhibition of Basolateral K⁺ Conductance in Human Airway Epithelial Cells

Apical adenosine regulates basolateral Ca²⁺-activated potassium channels in human airway Calu-3 epithelial cells