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

Masami Son, Yasushi Ito, Shinji Sato, Takayuki Ishikawa, Masashi Kondo, Shinsuke Nakayama, Kaoru Shimokata, Hiroaki Kume

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The present study investigated mechanisms underlying apical and basolateral P2Y1-mediated Cl- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (Isc) with different properties via P2Y1 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, ADPβS, and ATP-γS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc, 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 Ca2+ 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 Ca2+ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the Isc and the basolateral K+ current rather than the apical Cl- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 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.

Original languageEnglish
Pages (from-to)411-419
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number3
DOIs
Publication statusPublished - 01-03-2004

Fingerprint

Anions
Epithelium
Adenosine Triphosphate
Type C Phospholipases
Purinergic P2Y1 Receptors
Short circuit currents
Phosphatidylcholines
Adenylyl Cyclases
Bridge clearances
Charybdotoxin
Mucociliary Clearance
Nystatin
Ethane
Chelating Agents
Phosphatidylinositols
Adenosine Diphosphate
Esters
Epithelial Cells
Acids

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Son, Masami ; Ito, Yasushi ; Sato, Shinji ; Ishikawa, Takayuki ; Kondo, Masashi ; Nakayama, Shinsuke ; Shimokata, Kaoru ; Kume, Hiroaki. / Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia. In: American Journal of Respiratory Cell and Molecular Biology. 2004 ; Vol. 30, No. 3. pp. 411-419.
@article{ae2669bbf3f64dcd99a864eae041109d,
title = "Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia",
abstract = "The present study investigated mechanisms underlying apical and basolateral P2Y1-mediated Cl- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (Isc) with different properties via P2Y1 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, ADPβS, and ATP-γS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc, 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 Ca2+ 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 Ca2+ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the Isc and the basolateral K+ current rather than the apical Cl- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 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.",
author = "Masami Son and Yasushi Ito and Shinji Sato and Takayuki Ishikawa and Masashi Kondo and Shinsuke Nakayama and Kaoru Shimokata and Hiroaki Kume",
year = "2004",
month = "3",
day = "1",
doi = "10.1165/rcmb.2003-0183OC",
language = "English",
volume = "30",
pages = "411--419",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "3",

}

Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia. / Son, Masami; Ito, Yasushi; Sato, Shinji; Ishikawa, Takayuki; Kondo, Masashi; Nakayama, Shinsuke; Shimokata, Kaoru; Kume, Hiroaki.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 30, No. 3, 01.03.2004, p. 411-419.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

AU - Son, Masami

AU - Ito, Yasushi

AU - Sato, Shinji

AU - Ishikawa, Takayuki

AU - Kondo, Masashi

AU - Nakayama, Shinsuke

AU - Shimokata, Kaoru

AU - Kume, Hiroaki

PY - 2004/3/1

Y1 - 2004/3/1

N2 - The present study investigated mechanisms underlying apical and basolateral P2Y1-mediated Cl- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (Isc) with different properties via P2Y1 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, ADPβS, and ATP-γS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc, 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 Ca2+ 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 Ca2+ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the Isc and the basolateral K+ current rather than the apical Cl- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 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.

AB - The present study investigated mechanisms underlying apical and basolateral P2Y1-mediated Cl- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (Isc) with different properties via P2Y1 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, ADPβS, and ATP-γS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc, 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 Ca2+ 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 Ca2+ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the Isc and the basolateral K+ current rather than the apical Cl- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 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.

UR - http://www.scopus.com/inward/record.url?scp=1542345025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542345025&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2003-0183OC

DO - 10.1165/rcmb.2003-0183OC

M3 - Article

C2 - 12972400

AN - SCOPUS:1542345025

VL - 30

SP - 411

EP - 419

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 3

ER -