Interstitial cells of Cajal are involved in the afferent limb of the rectoanal inhibitory reflex
Interstitial cells of Cajal are involved in the afferent limb of the rectoanal inhibitory reflex
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DOI：
10.1136/gut.2004.051045
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发表时间：
2005-08-01
期刊：
影响因子：
24.5
通讯作者：
Boeckxstaens, GE
中科院分区：
文献类型：
--
作者：
de Lorijn, F;de Jonge, WJ;Boeckxstaens, GE
背景和目的：卡哈尔间质细胞(interstitial cell of Cajal，ICC)参与下食道括约肌和幽门的氮能神经传递。在此，我们研究了ICC和一氧化氮(NO)在小鼠肛门内括约肌(IAS)抑制性神经传递中的作用。方法：测定对照组、KITW/KITWv小鼠和神经元型一氧化氮合酶(NNOS)缺陷小鼠直肠肛门抑制反射、直肠顺应性和对电刺激的松弛。此外，我们还评价了N-硝基-L-精氨酸甲酯对神经元型一氧化氮合酶的阻断作用。结果：对照组iAS中KIT阳性ICC呈致密网状分布，而KITW/KITWv小鼠中未见。电刺激引起的IAS肌条松弛在nNOS2/2小鼠中减弱，而在KITW/KITWv小鼠中没有。阻断一氧化氮合酶可降低两种小鼠IAS肌条的松弛。在KITW/KITWv小鼠和nNOS缺陷小鼠中，IAS对直肠扩张的松弛作用明显减弱。体内阻断一氧化氮合酶可减弱对照组IAS的松弛。结论：iAS的抑制性神经支配和直肠肛管抑制性反射是由NO介导的，直肠肛管抑制性反射需要iAS内完整的ICC网络。因此，氮能神经支配的丧失和ICC的缺乏都会导致肛门松弛受损，并可能在直肠排空障碍中发挥重要作用。
Background and aims: Interstitial cells of Cajal (ICC) have been shown to be involved in nitrergic neurotransmission of the lower oesophageal sphincter and pylorus. Here we studied the role of ICC and nitric oxide ( NO) in the inhibitory neurotransmission of the murine internal anal sphincter (IAS).Methods: The rectoanal inhibitory reflex, rectal compliance, and relaxation of the isolated IAS to electrical stimulation were measured in controls, KITW/KITWv mice, and neuronal NO synthase ( nNOS) deficient mice. In addition, we evaluated the effect of blockade of nNOS using N-nitro-L-arginine methyl ester. Distribution of nNOS positive neurones and ICC in the IAS was assessed immunohistochemically.Results: KIT positive ICC were present in a dense network in the IAS of controls but not in KITW/KITWv mice. Relaxation of IAS muscle strips induced by electrical stimulation was diminished in nNOS2/ 2 mice but not in KITW/KITWv mice. Blockade of NOS reduced the relaxation of IAS muscle strips in both mice. Relaxation of the IAS to rectal distension was significantly diminished in KITW/ KITWv mice and nNOS deficient mice. In concert, in vivo blockade of NOS attenuated the relaxation of the IAS in controls. No significant difference in compliance was found.Conclusion: The inhibitory innervation of the IAS and the rectoanal inhibitory reflex are mediated by NO and the rectoanal inhibitory reflex requires an intact network of ICC in the IAS. Thus both loss of nitrergic innervation and deficiency of ICC lead to impaired anal relaxation and may play an important role in rectal evacuation disorders.