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

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28 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

All Science Journal Classification (ASJC) codes

  • Pharmacology

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