Deoxycholic acid inhibits pacemaker currents by activating ATP‐dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestine

Deoxycholic acid inhibits pacemaker currents by activating ATP‐dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestine
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脱氧胆酸通过前列腺素 E2 激活小鼠小肠 Cajal 间质细胞中 ATP 依赖性 K+ 通道,从而抑制起搏器电流

DOI:
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发表时间:
2005
影响因子:
7.3
通讯作者:
H. You
H. You
中科院分区:
医学2区
文献类型:
--
作者:
J. Jun;Seok Choi;I. Chang;Cha Kyung Yoon;H. Jeong;I. Kong;I. So;K. Kim;H. You

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1我们使用全细胞膜片钳技术在30°C下在培养的小鼠小肠Cajal间质细胞(ICC)中研究了脱氧胆酸在起搏电流中的作用。2去氧胆酸处理ICC后,起搏电流的频率和幅度降低,静息外向电流增加。此外,在电流钳制下,脱氧胆酸产生超极化的膜电位和起搏电位的幅度降低。3观察到的脱氧胆酸对起搏电流和起搏电位的影响完全被格列本脲(一种ATP敏感性K+通道阻滞剂)抑制。4 NS-398是一种特异性环氧合酶-2(考克斯-2)抑制剂,可显著抑制脱氧胆酸诱导的效应。前列腺素E2(PGE 2)的治疗导致起搏电流的幅度和频率的下降,并增加静息外向电流,这些观察到的PGE 2的影响被格列本脲阻断。5我们接下来检查了脱氧胆酸在ICC中PGE 2产生中的作用,发现脱氧胆酸通过诱导考克斯-2酶活性及其基因表达来增加PGE 2的产生。6结果表明,脱氧胆酸通过产生PGE 2激活ATP敏感性K+通道抑制ICC的起搏电流。
1 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. 2 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. 3 These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP‐sensitive K+ channel blocker. 4 NS‐398, a specific cyclooxygenase‐2 (COX‐2) inhibitor, significantly inhibited the deoxycholic acid‐induced effects. The treatment with prostaglandin E2 (PGE2) 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 PGE2 were blocked by glibenclamide. 5 We next examined the role of deoxycholic acid in the production of PGE2 in ICC, and found that deoxycholic acid increased PGE2 production through the induction of COX‐2 enzyme activity and its gene expression. 6 The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP‐sensitive K+ channels through the production of PGE2.
DOI: 10.1016/0016-5085(95)90585-5
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