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首页> 外文期刊>Life sciences >Action of imipramine on activated ATP-sensitive K(+) channels in interstitial cells of Cajal from murine small intestine.
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Action of imipramine on activated ATP-sensitive K(+) channels in interstitial cells of Cajal from murine small intestine.

机译：丙咪嗪对小鼠小肠Cajal间质细胞中激活的ATP敏感K（+）通道的作用。

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Tricyclic antidepressants have been widely used for the treatment of depression and as a therapeutic agent for the altered gastrointestinal (GI) motility of irritable bowel syndrome (IBS). The aim of this study was to clarify whether antidepressants directly modulate pacemaker currents in cultured interstitial cells of Cajal (ICC). We used the whole-cell patch-clamp techniques at 30 degrees C in cultured ICC from the mouse small intestine. Treatment of pinacidil, an ATP-sensitive K(+) channel opener, in the ICC using the current clamping mode, produced hyperpolarization of the membrane potential and decreased the amplitude of the pacemaker potentials. With the voltage clamp mode, we observed a decrease in the frequency and amplitude of pacemaker currents and increases in the resting outward currents. These effects of pinacidil on pacemaker potentials and currents were completely suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. Also, with the current clamp mode, imipramine blocked theaffect of pinacidil on the pacemaker potentials. Observations of the voltage clamp mode with imipramine, desipramine and amitryptyline suppressed the action of pinacidil in the ICC. Next, we examined whether protein kinase C (PKC) and the G protein are involved in the action of imipramine on pinacidil induced pacemaker current inhibition. We used chelerythrine, a potent PKC inhibitor and GDPbetaS, a nonhydrolyzable guanosine 5-diphosphate (GDP) analogue that permanently inactivates GTP-binding proteins. We found that pretreatment with chelerythrine and intracellular application of GDPbetaS had no influence on the blocking action of imipramine on inhibited pacemaker currents by pinacidil. We conclude that imipramine inhibited the activated ATP-sensitive K(+) channels in ICC. This action does not appear to be mediated through the G protein and protein kinase C. Furthermore, this study may suggest another possible mechanism for tricyclic antidepressants related modulation of GI motility.
机译：三环抗抑郁药已广泛用于治疗抑郁症，并作为肠易激综合症（IBS）胃肠道（GI）运动改变的治疗剂。这项研究的目的是阐明抗抑郁药是否直接调节培养的Cajal间质细胞（ICC）中的起搏器电流。我们在小鼠小肠培养的ICC中于30摄氏度使用了全细胞膜片钳技术。使用电流钳位模式在ICC中治疗pinacidil（一种ATP敏感的K（+）通道开放剂）可产生膜电位的超极化作用，并降低起搏器电位的幅度。在电压钳模式下，我们观察到起搏器电流的频率和幅度降低，而静止的向外电流则增加。吡那地尔对起搏器电位和电流的这些作用已被格列本脲（一种ATP敏感的K（+）通道阻滞剂）完全抑制。同样，在电流钳模式下，丙咪嗪阻止了吡那地尔对起搏器电位的影响。用丙咪嗪，地昔帕明和阿米替林对电压钳模式的观察抑制了吡那地尔在ICC中的作用。接下来，我们检查了蛋白激酶C（PKC）和G蛋白是否参与了丙咪嗪对吡那地尔诱导的起搏器电流抑制的作用。我们使用了有效的PKC抑制剂白屈菜红碱和永久性失活GTP结合蛋白的不可水解鸟苷5-二磷酸（GDP）类似物GDPbetaS。我们发现用白屈菜红碱预处理和胞内施用GDPbetaS不会对丙咪嗪对吡那地尔抑制起搏电流的阻断作用产生影响。我们得出的结论是，丙咪嗪在ICC中抑制了激活的ATP敏感性K（+）通道。该作用似乎不是通过G蛋白和蛋白激酶C介导的。此外，这项研究可能暗示了三环抗抑郁药与GI运动调节相关的另一种可能机制。

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