Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels

Christiana Dimitropoulou, E. White, Dennis Randall Ownby, John D. Catravas

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Both the incidence and severity of asthma in women are influenced by fluctuations in estrogen (E2) levels, raising the possibility that E2s may reduce the hyperresponsiveness that is characteristic of asthma. We examined the effect of E2 and its downstream signaling pathways in isolated mouse bronchial and tracheal rings passively sensitized either with serum from patients with atopic asthma (ATR) or with serum from control subjects (CTR). ATR exhibited significantly higher sensitivity to carbachol than CTR. Pretreatment of ATR with E2 shifted the carbachol concentration-response curve (CCRC) toward that of CTR. The E2 effect was abolished by the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, the soluble guanyl cyclase inhibitor, quinoxalin-1, or the protein kinase C inhibitor, KT5823. Inhibition of the large-conductance, calcium-activated potassium (BKCa) channel activity with iberiotoxin also attenuated the E2 effect on ATR. In patch-clamp studies, E2 increased by 50-fold the BKCa, channel activity in freshly isolated airway smooth muscle cells. This increase was completely blocked by KT5823. These studies suggest that, at physiologic concentrations, E2 can prevent cholinergic-induced constriction of asthmatic tracheal rings by activating the nitric oxide-cGMP-protein kinase G pathway to increase BKCa channel activity.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2005

Fingerprint

Calcium-Activated Potassium Channels
Carbachol
Constriction
Estrogens
Asthma
Electric potential
Large-Conductance Calcium-Activated Potassium Channels
Cyclic GMP-Dependent Protein Kinases
Quinoxalines
Protein C Inhibitor
Guanylate Cyclase
Nitroarginine
Clamping devices
Protein Kinase Inhibitors
Serum
Nitric Oxide Synthase
Protein Kinase C
Cholinergic Agents
Smooth Muscle Myocytes
Muscle

Keywords

  • Airway smooth muscle
  • Asthma
  • Estrogen
  • Large conductance voltage and calcium-dependent potassium channels
  • Nitric oxide

ASJC Scopus subject areas

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

Cite this

Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels. / Dimitropoulou, Christiana; White, E.; Ownby, Dennis Randall; Catravas, John D.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 32, No. 3, 01.03.2005, p. 239-247.

Research output: Contribution to journalArticle

@article{148dad7917ec453ab641d2614a8d1d40,
title = "Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels",
abstract = "Both the incidence and severity of asthma in women are influenced by fluctuations in estrogen (E2) levels, raising the possibility that E2s may reduce the hyperresponsiveness that is characteristic of asthma. We examined the effect of E2 and its downstream signaling pathways in isolated mouse bronchial and tracheal rings passively sensitized either with serum from patients with atopic asthma (ATR) or with serum from control subjects (CTR). ATR exhibited significantly higher sensitivity to carbachol than CTR. Pretreatment of ATR with E2 shifted the carbachol concentration-response curve (CCRC) toward that of CTR. The E2 effect was abolished by the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, the soluble guanyl cyclase inhibitor, quinoxalin-1, or the protein kinase C inhibitor, KT5823. Inhibition of the large-conductance, calcium-activated potassium (BKCa) channel activity with iberiotoxin also attenuated the E2 effect on ATR. In patch-clamp studies, E2 increased by 50-fold the BKCa, channel activity in freshly isolated airway smooth muscle cells. This increase was completely blocked by KT5823. These studies suggest that, at physiologic concentrations, E2 can prevent cholinergic-induced constriction of asthmatic tracheal rings by activating the nitric oxide-cGMP-protein kinase G pathway to increase BKCa channel activity.",
keywords = "Airway smooth muscle, Asthma, Estrogen, Large conductance voltage and calcium-dependent potassium channels, Nitric oxide",
author = "Christiana Dimitropoulou and E. White and Ownby, {Dennis Randall} and Catravas, {John D.}",
year = "2005",
month = "3",
day = "1",
doi = "10.1165/rcmb.2004-0331OC",
language = "English (US)",
volume = "32",
pages = "239--247",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "3",

}

TY - JOUR

T1 - Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels

AU - Dimitropoulou, Christiana

AU - White, E.

AU - Ownby, Dennis Randall

AU - Catravas, John D.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - Both the incidence and severity of asthma in women are influenced by fluctuations in estrogen (E2) levels, raising the possibility that E2s may reduce the hyperresponsiveness that is characteristic of asthma. We examined the effect of E2 and its downstream signaling pathways in isolated mouse bronchial and tracheal rings passively sensitized either with serum from patients with atopic asthma (ATR) or with serum from control subjects (CTR). ATR exhibited significantly higher sensitivity to carbachol than CTR. Pretreatment of ATR with E2 shifted the carbachol concentration-response curve (CCRC) toward that of CTR. The E2 effect was abolished by the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, the soluble guanyl cyclase inhibitor, quinoxalin-1, or the protein kinase C inhibitor, KT5823. Inhibition of the large-conductance, calcium-activated potassium (BKCa) channel activity with iberiotoxin also attenuated the E2 effect on ATR. In patch-clamp studies, E2 increased by 50-fold the BKCa, channel activity in freshly isolated airway smooth muscle cells. This increase was completely blocked by KT5823. These studies suggest that, at physiologic concentrations, E2 can prevent cholinergic-induced constriction of asthmatic tracheal rings by activating the nitric oxide-cGMP-protein kinase G pathway to increase BKCa channel activity.

AB - Both the incidence and severity of asthma in women are influenced by fluctuations in estrogen (E2) levels, raising the possibility that E2s may reduce the hyperresponsiveness that is characteristic of asthma. We examined the effect of E2 and its downstream signaling pathways in isolated mouse bronchial and tracheal rings passively sensitized either with serum from patients with atopic asthma (ATR) or with serum from control subjects (CTR). ATR exhibited significantly higher sensitivity to carbachol than CTR. Pretreatment of ATR with E2 shifted the carbachol concentration-response curve (CCRC) toward that of CTR. The E2 effect was abolished by the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, the soluble guanyl cyclase inhibitor, quinoxalin-1, or the protein kinase C inhibitor, KT5823. Inhibition of the large-conductance, calcium-activated potassium (BKCa) channel activity with iberiotoxin also attenuated the E2 effect on ATR. In patch-clamp studies, E2 increased by 50-fold the BKCa, channel activity in freshly isolated airway smooth muscle cells. This increase was completely blocked by KT5823. These studies suggest that, at physiologic concentrations, E2 can prevent cholinergic-induced constriction of asthmatic tracheal rings by activating the nitric oxide-cGMP-protein kinase G pathway to increase BKCa channel activity.

KW - Airway smooth muscle

KW - Asthma

KW - Estrogen

KW - Large conductance voltage and calcium-dependent potassium channels

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=15044340297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15044340297&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2004-0331OC

DO - 10.1165/rcmb.2004-0331OC

M3 - Article

VL - 32

SP - 239

EP - 247

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 3

ER -