Absence of peristalsis in the ileum of W/WV mutant mice that are selectively deficient in myenteric interstitial cells of Cajal

Absence of peristalsis in the ileum of W/WV mutant mice that are selectively deficient in myenteric interstitial cells of Cajal
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DOI:
10.1540/jsmr.41.141
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发表时间:
2005-06-01
影响因子:
--
通讯作者:
Takaki, Miyako
Takaki, Miyako
中科院分区:
其他
文献类型:
--
作者:
Nakagawa, Tadashi;Misawa, Hiromi;Takaki, Miyako

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众所周知,肠神经系统在胃肠蠕动运动的产生中起着关键作用。近年来,研究发现Cajal间质细胞(ICC)网络在自发性胃肠运动的发生中起重要作用。然而,ICC在蠕动运动产生机制中的作用仍存在争议。本研究的目的是揭示起搏器肌间ICC(ICC-MY)和肠神经系统如何参与肠道炎症的发生机制。我们比较了野生型(WT)小鼠与选择性缺乏ICC-MY的W/W-V突变小鼠的回肠自发蠕动运动。在0-0.5 cm H2O的静水压力下,从4 cm长的回肠段的环肌和纵肌同时进行记录。在对照条件下,在N-硝基-L-精氨酸甲酯(L-NAME)存在下和在河豚毒素(TTX)后,比较WT和W/W-V突变小鼠之间回肠的机械活动和连续视频图像。在WT小鼠回肠中,经常观察到蠕动波从口腔传播到肛门末端。这些蠕动波的频率及其相关的同步纵向和环形肌肉收缩增加L-NAME。TTX可使蠕动波消失。在W/W-V突变小鼠回肠,没有蠕动波传播从口腔到肛门端观察到控制,甚至L-NAME后,虽然局部自发产生的纵向和环形肌肉收缩增强L-NAME。这些局部收缩并没有被M废除。结果表明,ICC-MY对自发性肠蠕动的产生是必不可少的。可以想象的是,ICC-MY可以确定肠道兴奋的极性,使得纵向和环形肌肉收缩从肠段的口腔端传播到肛门端,尽管为什么ICC-MY对于神经通路是必要的问题仍然没有得到解决。
It is well known that the enteric nervous system plays a key role in the generation of gastrointestinal peristaltic movements. Recently, the networks of interstitial cells of Cajal (ICC) have been found to be essential in the generation of spontaneous gastrointestinal movements. However, the role of ICC in the mechanisms involved in the generation of peristaltic movements is still controversial. The aim of the present study was to reveal how pacemaker myenteric ICC (ICC-MY) and the enteric nervous system contribute to the mechanisms involved in the generation of intestinal peristalsis. We compared spontaneous peristaltic movements of the ileum in wild type (WT) mice with those in W/W-V mutant mice which are selectively deficient in ICC-MY. Simultaneous recordings were made from both the circular and longitudinal muscle of a 4-cm long segment of ileum under hydrostatic pressure of 0-0.5 cm H2O. Mechanical activity and continuous video-images of the ileum were compared between WT and W/W-V mutant mice under control conditions, in the presence of N-nitro-L-arginine methyl ester (L-NAME) and after tetrodotoxin (TTX). In the WT mouse ileum, peristaltic waves to propagate from the oral to the anal end were frequently observed. The frequency of these peristaltic waves and their associated synchronous longitudinal and circular muscle contractions was increased by L-NAME. The peristaltic waves were abolished by TTX. In the W/W-V mutant mouse ileum, no peristaltic waves to propagate from the oral to the anal end were observed in control and even after L-NAME, although the local spontaneously generated longitudinal and circular muscle contractions were enhanced by L-NAME. These local contractions were not abolished by M. The results presented here suggested that ICC-MY are essential for the generation of spontaneous intestinal peristaltic movements. It is conceivable that ICC-MY may determine the polarity of the excitation of the intestine such that longitudinal and circular muscle contractions propagate from the oral to the anal end of the intestinal segments, although the question of why ICC-MY are necessary for the neural pathways remains unresolved.