Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K + channels through prostaglandin E 2 in interstitial cells of Cajal from the murine small intestine

Jae Yeoul Jun, Seok Choi, In Youb Chang, Cha Kyung Yoon, Hye Gwang Jeong, Indeok Kong, Insuk So, Ki Whan Elm, Ho Jin You

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K + channel blocker. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E 2 (PGE 2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE 2 were blocked by glibenclamide. We next examined the role of deoxycholic acid in the production of PGE 2 in ICC, and found that deoxycholic acid increased PGE 2 production through the induction of COX-2 enzyme activity and its gene expression. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K + channels through the production of PGE 2.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalBritish Journal of Pharmacology
Volume144
Issue number2
DOIs
Publication statusPublished - 2005 Jan 1

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Interstitial Cells of Cajal
Deoxycholic Acid
Prostaglandins E
Small Intestine
Adenosine Triphosphate
Glyburide
Cyclooxygenase 2 Inhibitors
Patch-Clamp Techniques
Cyclooxygenase 2
Constriction
Membrane Potentials
Cultured Cells
Gene Expression

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Jun, Jae Yeoul ; Choi, Seok ; Chang, In Youb ; Yoon, Cha Kyung ; Jeong, Hye Gwang ; Kong, Indeok ; So, Insuk ; Elm, Ki Whan ; You, Ho Jin. / Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K + channels through prostaglandin E 2 in interstitial cells of Cajal from the murine small intestine. In: British Journal of Pharmacology. 2005 ; Vol. 144, No. 2. pp. 242-251.
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abstract = "We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K + channel blocker. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E 2 (PGE 2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE 2 were blocked by glibenclamide. We next examined the role of deoxycholic acid in the production of PGE 2 in ICC, and found that deoxycholic acid increased PGE 2 production through the induction of COX-2 enzyme activity and its gene expression. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K + channels through the production of PGE 2.",
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Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K + channels through prostaglandin E 2 in interstitial cells of Cajal from the murine small intestine. / Jun, Jae Yeoul; Choi, Seok; Chang, In Youb; Yoon, Cha Kyung; Jeong, Hye Gwang; Kong, Indeok; So, Insuk; Elm, Ki Whan; You, Ho Jin.

In: British Journal of Pharmacology, Vol. 144, No. 2, 01.01.2005, p. 242-251.

Research output: Contribution to journalArticle

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AU - Jun, Jae Yeoul

AU - Choi, Seok

AU - Chang, In Youb

AU - Yoon, Cha Kyung

AU - Jeong, Hye Gwang

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AU - So, Insuk

AU - Elm, Ki Whan

AU - You, Ho Jin

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N2 - We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K + channel blocker. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E 2 (PGE 2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE 2 were blocked by glibenclamide. We next examined the role of deoxycholic acid in the production of PGE 2 in ICC, and found that deoxycholic acid increased PGE 2 production through the induction of COX-2 enzyme activity and its gene expression. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K + channels through the production of PGE 2.

AB - We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K + channel blocker. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E 2 (PGE 2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE 2 were blocked by glibenclamide. We next examined the role of deoxycholic acid in the production of PGE 2 in ICC, and found that deoxycholic acid increased PGE 2 production through the induction of COX-2 enzyme activity and its gene expression. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K + channels through the production of PGE 2.

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