Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Korea.
Mol Cells. 2011 Aug;32(2):153-60. doi: 10.1007/s10059-011-1019-1. Epub 2011 May 20.
The interstitial cells of Cajal (ICCs) are pacemakers in the gastrointestinal tract and transient receptor potential melastatin type 7 (TRPM7) is a candidate for pacemaker channels. The effect of the 5-lipoxygenase (5-LOX) inhibitors NDGA, AA861, MK886 and zileuton on pacemaking activity of ICCs was examined using the whole cell patch clamp technique. NDGA and AA861 decreased the amplitude of pacemaker potentials in ICC clusters, but the resting membrane potentials displayed little change, respectively. Also, perfusing NDGA and AA861 into the bath reduced both inward current and outward current in TRPM7-like current in single ICC, respectively. But, they had no effects on Ca(2+) activated Cl(-) currents. The 5-LOX inhibitors MK886 and zileuton were, however, ineffective in pacemaker potentials in ICC clusters and in TRPM7-like current in single ICC, respectively. A specific TRPC3 inhibitor, pyrazole compound (Pyr3), and a specific TRPM4 inhibitor, 9-phenanthrol, had no effects in pacemaker potentials in ICC clusters and in TRPM7-like current in single ICC. These results suggest that, among the tested 5-LOX inhibitors, NDGA and AA861 modulate the pacemaker activities of the ICCs, and that the TRPM7 channel can affect intestinal motility.
Cajal 间质细胞(ICCs)是胃肠道中的起搏细胞,而瞬时受体电位 melastatin 型 7(TRPM7)是起搏通道的候选者。使用全细胞膜片钳技术研究了 5-脂氧合酶(5-LOX)抑制剂 NDGA、AA861、MK886 和 zileuton 对 ICCs 起搏活动的影响。NDGA 和 AA861 分别降低了 ICC 簇中的起搏电位幅度,但静息膜电位变化不大。此外,将 NDGA 和 AA861 灌注到浴中,分别减少了单个 ICC 中的 TRPM7 样电流中的内向电流和外向电流。但是,它们对 Ca(2+)激活的 Cl(-)电流没有影响。5-LOX 抑制剂 MK886 和 zileuton 分别对 ICC 簇中的起搏电位和单个 ICC 中的 TRPM7 样电流没有作用。一种特定的 TRPC3 抑制剂,吡唑化合物(Pyr3)和一种特定的 TRPM4 抑制剂,9-菲咯啉,对 ICC 簇中的起搏电位和单个 ICC 中的 TRPM7 样电流没有影响。这些结果表明,在所测试的 5-LOX 抑制剂中,NDGA 和 AA861 调节 ICC 的起搏活动,而 TRPM7 通道可以影响肠道蠕动。