Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BKCa channel activity in cultured endothelial cells of human coronary artery

研究成果: Article

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摘要

ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K+ outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17β-estradiol. Under current-clamp condition, ICI-182,780 (3μM) depolarized the membrane potentials of the cells, and magnolol (10μM) or nordihydroguaiaretic acid (10μM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca2+-activated K+ channels (BKCa channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC50 value of 3μM. After BKCa channel activity was suppressed by 2-methoxyestradiol (3μM), subsequent application of ICI-182,780 (3μM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BKCa channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC50 value of 2μM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BKCa channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BKCa channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

原文English
頁(從 - 到)2053-2063
頁數11
期刊Biochemical Pharmacology
66
發行號10
DOIs
出版狀態Published - 2003 十一月 15

指紋

Endothelial cells
Cultured Cells
Coronary Vessels
Endothelial Cells
Masoprocol
Estrogen Receptor Antagonists
fulvestrant
Inhibitory Concentration 50
Calcium-Activated Potassium Channels
Depolarization
Clamping devices
Patch-Clamp Techniques
Baths
Estrogen Receptors
Membrane Potentials
Smooth Muscle Myocytes
Muscle
Estradiol
Estrogens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

引用此文

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title = "Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BKCa channel activity in cultured endothelial cells of human coronary artery",
abstract = "ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K+ outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17β-estradiol. Under current-clamp condition, ICI-182,780 (3μM) depolarized the membrane potentials of the cells, and magnolol (10μM) or nordihydroguaiaretic acid (10μM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca2+-activated K+ channels (BKCa channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC50 value of 3μM. After BKCa channel activity was suppressed by 2-methoxyestradiol (3μM), subsequent application of ICI-182,780 (3μM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BKCa channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC50 value of 2μM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BKCa channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BKCa channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.",
author = "Yen-Chin Liu and Lo, {Yi Ching} and Chin-Wei Huang and Sheng-Nan Wu",
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T1 - Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BKCa channel activity in cultured endothelial cells of human coronary artery

AU - Liu, Yen-Chin

AU - Lo, Yi Ching

AU - Huang, Chin-Wei

AU - Wu, Sheng-Nan

PY - 2003/11/15

Y1 - 2003/11/15

N2 - ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K+ outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17β-estradiol. Under current-clamp condition, ICI-182,780 (3μM) depolarized the membrane potentials of the cells, and magnolol (10μM) or nordihydroguaiaretic acid (10μM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca2+-activated K+ channels (BKCa channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC50 value of 3μM. After BKCa channel activity was suppressed by 2-methoxyestradiol (3μM), subsequent application of ICI-182,780 (3μM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BKCa channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC50 value of 2μM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BKCa channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BKCa channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

AB - ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K+ outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17β-estradiol. Under current-clamp condition, ICI-182,780 (3μM) depolarized the membrane potentials of the cells, and magnolol (10μM) or nordihydroguaiaretic acid (10μM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca2+-activated K+ channels (BKCa channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC50 value of 3μM. After BKCa channel activity was suppressed by 2-methoxyestradiol (3μM), subsequent application of ICI-182,780 (3μM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BKCa channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC50 value of 2μM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BKCa channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BKCa channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

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