Fenamates stimulate BKCa channel activity in the human osteoblast-like MG-63 cells

Sheng-Nan Wu, C. R. Jan, H. T. Chiang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: The fenamates, a family of nonsteroidal antiinflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood. Methods: The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique. Results: In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (IK). The niflumic acid-stimulated IK was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. The EC50 values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCa channels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCa channels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it. Conclusions: The fenamates can stimulate BKCa channel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCa channel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.

Original languageEnglish
Pages (from-to)522-533
Number of pages12
JournalJournal of Investigative Medicine
Volume49
Issue number6
Publication statusPublished - 2001 Jan 1

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Fenamates
Niflumic Acid
Osteoblasts
Human Activities
Meclofenamic Acid
Chemical activation
nimesulide
Flufenamic Acid
Masoprocol
Apamin
Membranes
Piroxicam
Calcium-Activated Potassium Channels
Evans Blue
Cyclooxygenase Inhibitors
Glyburide
Clamping devices
Patch-Clamp Techniques
Baths
Indomethacin

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Fenamates stimulate BKCa channel activity in the human osteoblast-like MG-63 cells",
abstract = "Background: The fenamates, a family of nonsteroidal antiinflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood. Methods: The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique. Results: In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (IK). The niflumic acid-stimulated IK was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. The EC50 values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCa channels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCa channels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it. Conclusions: The fenamates can stimulate BKCa channel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCa channel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.",
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Fenamates stimulate BKCa channel activity in the human osteoblast-like MG-63 cells. / Wu, Sheng-Nan; Jan, C. R.; Chiang, H. T.

In: Journal of Investigative Medicine, Vol. 49, No. 6, 01.01.2001, p. 522-533.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fenamates stimulate BKCa channel activity in the human osteoblast-like MG-63 cells

AU - Wu, Sheng-Nan

AU - Jan, C. R.

AU - Chiang, H. T.

PY - 2001/1/1

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N2 - Background: The fenamates, a family of nonsteroidal antiinflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood. Methods: The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique. Results: In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (IK). The niflumic acid-stimulated IK was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. The EC50 values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCa channels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCa channels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it. Conclusions: The fenamates can stimulate BKCa channel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCa channel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.

AB - Background: The fenamates, a family of nonsteroidal antiinflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood. Methods: The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique. Results: In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (IK). The niflumic acid-stimulated IK was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. The EC50 values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCa channels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCa channels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it. Conclusions: The fenamates can stimulate BKCa channel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCa channel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.

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