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 language | English |
|---|---|
| Pages (from-to) | 188-199 |
| Number of pages | 12 |
| Journal | Journal of Cellular Physiology |
| Volume | 192 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2002 Jul 20 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
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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 journal › Article
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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U2 - 10.1002/jcp.10127
DO - 10.1002/jcp.10127
M3 - Article
C2 - 12115725
AN - SCOPUS:0035983481
VL - 192
SP - 188
EP - 199
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 2
ER -