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; In Deok Kong; Insuk So; Ki Whan Elm; Ho Jin You

doi:10.1038/sj.bjp.0706074

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, In Deok Kong, Insuk So, Ki Whan Elm, Ho Jin You

Physiology

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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.

Original language	English
Pages (from-to)	242-251
Number of pages	10
Journal	British Journal of Pharmacology
Volume	144
Issue number	2
DOIs	https://doi.org/10.1038/sj.bjp.0706074
Publication status	Published - 2005 Jan

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Pharmacology

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10.1038/sj.bjp.0706074

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Jun, J. Y., Choi, S., Chang, I. Y., Yoon, C. K., Jeong, H. G., Kong, I. D., So, I., Elm, K. W., & You, H. J. (2005). 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. British Journal of Pharmacology, 144(2), 242-251. https://doi.org/10.1038/sj.bjp.0706074

@article{7e6c0817b04c429ca6aaefd490816a04,

title = "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",

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.",

author = "Jun, {Jae Yeoul} and Seok Choi and Chang, {In Youb} and Yoon, {Cha Kyung} and Jeong, {Hye Gwang} and Kong, {In Deok} and Insuk So and Elm, {Ki Whan} and You, {Ho Jin}",

year = "2005",

month = jan,

doi = "10.1038/sj.bjp.0706074",

language = "English",

volume = "144",

pages = "242--251",

journal = "British Journal of Pharmacology",

issn = "0007-1188",

publisher = "Wiley-Blackwell",

number = "2",

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Jun, JY, Choi, S, Chang, IY, Yoon, CK, Jeong, HG, Kong, ID, So, I, Elm, KW & You, HJ 2005, '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', British Journal of Pharmacology, vol. 144, no. 2, pp. 242-251. https://doi.org/10.1038/sj.bjp.0706074

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 et al.
In: British Journal of Pharmacology, Vol. 144, No. 2, 01.2005, p. 242-251.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Jun, Jae Yeoul

AU - Choi, Seok

AU - Chang, In Youb

AU - Yoon, Cha Kyung

AU - Jeong, Hye Gwang

AU - Kong, In Deok

AU - So, Insuk

AU - Elm, Ki Whan

AU - You, Ho Jin

PY - 2005/1

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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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JF - British Journal of Pharmacology

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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

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