首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Involvement of Thromboxane A2 in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine
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Involvement of Thromboxane A2 in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine

机译:血栓烷A2参与小鼠小肠Cajal间质细胞起搏器活性的调节

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Although many studies show that thromboxane A2 (TXA2) has the action of gastrointestinal (GI) motility using GI muscle cells and tissue, there are no reports on the effects of TXA2 on interstitial cells of Cajal (ICC) that function as pacemaker cells in GI tract. So, we studied the modulation of pacemaker activities by TXA2 in ICC with whole cell patch-clamp technique. Externally applied TXA2 (5μM) produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The tonic inward currents by TXA2 were inhibited by intracellular application of GDP-β-S. The pretreatment of ICC with Ca2+ free solution and thapsigargin, a Ca2+-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the TXA2-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the TXA2-induced effects on pacemaker currents. These results suggest that TXA2 can regulate intestinal motility through the modulation of ICC pacemaker activities. This modulation of pacemaker activities by TXA2 may occur by the activation of G protein and PKC independent pathway via extra and intracellular Ca2+ modulation.
机译:尽管许多研究表明血栓烷A 2 (TXA 2 )具有利用GI肌肉细胞和组织的胃肠运动(GI)的作用,但尚无关于这种作用的报道。 Cajal间质细胞(ICC)上的TXA 2 在胃肠道中起起搏器作用。因此,我们采用全细胞膜片钳技术研究了ICC中TXA 2 对起搏器活动的调节作用。外部施加的TXA 2 (5μM)在电流钳模式下使膜去极化,而在电压钳模式下使补剂内向起搏器电流增加。细胞内施用GDP-β-S抑制了TXA 2 的进补电流。用游离Ca 2 + 溶液和thapsigargin(内质网中的Ca 2 + -ATPase抑制剂)对ICC的预处理消除了起搏电流的产生并抑制了TXA 2 引起的滋补内向电流。然而,白屈菜红碱或钙磷蛋白C(蛋白激酶C抑制剂)并没有阻止TXA 2 对起搏电流的影响。这些结果表明,TXA 2 可以通过调节ICC起搏器活动来调节肠道运动。 TXA 2 对心脏起搏器活性的这种调节可能是通过额外的和细胞内的Ca 2 + 调节激活G蛋白和PKC独立途径而发生的。

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