Enhanced activity of Ca2+-activated K+ channels by 1-[2-hydroxy-3-propyl-4-[(1H-tetrazol-5-yl) butoxyl]phenyl] ethanone (LY-171883) in neuroendocrine and neuroblastoma cell lines

Ping Chia Li, Jin Tung Liang, Hung Tu Huang, Pei Hsuan Lin, Sheng-Nan Wu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH3 and in neuroblastoma IMR-32 cells. In GH3 cells, LY-171883 (1-300 μM) reversibly increased the amplitude of Ca2+-activated K+ current in a concentration-dependent manner with an EC50 value of 15 μM. In excised inside-out patches recorded from GH3 cells, the application of LY-171883 into cytosolic face did not modify single channel conductance of large-conductance Ca2+-activated K+ (BKCa) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 μM) suppressed the activity of BKCa channels and MK-571 (30 μM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 μM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH3 cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 μM) also stimulated BKCa channel activity in a voltage-dependent manner. However, neither clofibrate (30 μM) nor leukotriene D4 (10 μM) affected the channel activity in IMR-32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function.

Original languageEnglish
Pages (from-to)188-199
Number of pages12
JournalJournal of Cellular Physiology
Volume192
Issue number2
DOIs
Publication statusPublished - 2002 Jul 20

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LY 171883
Calcium-Activated Potassium Channels
Neuroendocrine Cells
Neuroblastoma
Cells
troglitazone
verlukast
Membranes
Cell Line
Leukotriene Receptors
Leukotriene D4
Leukotriene Antagonists
Clofibrate
Peroxisome Proliferator-Activated Receptors
Clamping devices
Electric potential
Membrane Potentials
Action Potentials

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

@article{31d267959c6642038038bb1d5aadda85,
title = "Enhanced activity of Ca2+-activated K+ channels by 1-[2-hydroxy-3-propyl-4-[(1H-tetrazol-5-yl) butoxyl]phenyl] ethanone (LY-171883) in neuroendocrine and neuroblastoma cell lines",
abstract = "The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH3 and in neuroblastoma IMR-32 cells. In GH3 cells, LY-171883 (1-300 μM) reversibly increased the amplitude of Ca2+-activated K+ current in a concentration-dependent manner with an EC50 value of 15 μM. In excised inside-out patches recorded from GH3 cells, the application of LY-171883 into cytosolic face did not modify single channel conductance of large-conductance Ca2+-activated K+ (BKCa) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 μM) suppressed the activity of BKCa channels and MK-571 (30 μM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 μM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH3 cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 μM) also stimulated BKCa channel activity in a voltage-dependent manner. However, neither clofibrate (30 μM) nor leukotriene D4 (10 μM) affected the channel activity in IMR-32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function.",
author = "Li, {Ping Chia} and Liang, {Jin Tung} and Huang, {Hung Tu} and Lin, {Pei Hsuan} and Sheng-Nan Wu",
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Enhanced activity of Ca2+-activated K+ channels by 1-[2-hydroxy-3-propyl-4-[(1H-tetrazol-5-yl) butoxyl]phenyl] ethanone (LY-171883) in neuroendocrine and neuroblastoma cell lines. / Li, Ping Chia; Liang, Jin Tung; Huang, Hung Tu; Lin, Pei Hsuan; Wu, Sheng-Nan.

In: Journal of Cellular Physiology, Vol. 192, No. 2, 20.07.2002, p. 188-199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhanced activity of Ca2+-activated K+ channels by 1-[2-hydroxy-3-propyl-4-[(1H-tetrazol-5-yl) butoxyl]phenyl] ethanone (LY-171883) in neuroendocrine and neuroblastoma cell lines

AU - Li, Ping Chia

AU - Liang, Jin Tung

AU - Huang, Hung Tu

AU - Lin, Pei Hsuan

AU - Wu, Sheng-Nan

PY - 2002/7/20

Y1 - 2002/7/20

N2 - The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH3 and in neuroblastoma IMR-32 cells. In GH3 cells, LY-171883 (1-300 μM) reversibly increased the amplitude of Ca2+-activated K+ current in a concentration-dependent manner with an EC50 value of 15 μM. In excised inside-out patches recorded from GH3 cells, the application of LY-171883 into cytosolic face did not modify single channel conductance of large-conductance Ca2+-activated K+ (BKCa) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 μM) suppressed the activity of BKCa channels and MK-571 (30 μM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 μM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH3 cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 μM) also stimulated BKCa channel activity in a voltage-dependent manner. However, neither clofibrate (30 μM) nor leukotriene D4 (10 μM) affected the channel activity in IMR-32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function.

AB - The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH3 and in neuroblastoma IMR-32 cells. In GH3 cells, LY-171883 (1-300 μM) reversibly increased the amplitude of Ca2+-activated K+ current in a concentration-dependent manner with an EC50 value of 15 μM. In excised inside-out patches recorded from GH3 cells, the application of LY-171883 into cytosolic face did not modify single channel conductance of large-conductance Ca2+-activated K+ (BKCa) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 μM) suppressed the activity of BKCa channels and MK-571 (30 μM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 μM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH3 cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 μM) also stimulated BKCa channel activity in a voltage-dependent manner. However, neither clofibrate (30 μM) nor leukotriene D4 (10 μM) affected the channel activity in IMR-32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function.

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