Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide-sensitive guanylate cyclase in the guinea-pig gastrointestinal tract
Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide-sensitive guanylate cyclase in the guinea-pig gastrointestinal tract
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DOI：
10.1016/j.neuroscience.2007.12.044
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发表时间：
2008-03-18
期刊：
影响因子：
3.3
通讯作者：
Nojyo, Y.
中科院分区：
文献类型：
--
作者：
Iino, S.;Horiglichi, K.;Nojyo, Y.
一氧化氮（NO）是胃肠道中的主要信号分子，并且释放的NO抑制肌肉收缩。NO的作用是通过刺激可溶性鸟苷酸环化酶（sGC，NO敏感性GC）和随后的cGMP浓度增加来介导的。为了阐明NO在胃肠道肌肉组织中的靶点，我们研究了sGC的β 1和α 1亚单位的免疫组织化学定位以及豚鼠胃肠道中含神经元型NO合酶（nNOS）的神经的分布。在Cajal间质细胞（ICC）、成纤维细胞样细胞（FLC）和肌肉组织中的肠神经元中观察到sGC β 1和sGC α 1的不同免疫反应性。使用抗c-Kit抗体和抗sGC β 1抗体的双重免疫组织化学显示，在整个胃肠道的几乎所有肌内ICC中都存在sGC β 1免疫反应性。免疫电镜显示sGC β 1免疫阳性细胞具有肌内ICC的一些标准：存在小窝;经常与神经束相关;与平滑肌细胞密切接触。sGC β 1免疫阳性ICC与肌层中含nNOS的神经纤维紧密贴壁。免疫组织化学和免疫电镜观察显示，FLC在肌肉组织中也显示sGC β 1免疫反应性。FLC常与nNOS免疫阳性神经纤维相关。在肌间层中，几乎所有的肌间神经节含有nNOS免疫阳性神经细胞，并被肌间ICC和FLC包围。大肠中的肌间ICC和整个胃肠道中的FLC在肌间层中显示sGC β 1免疫反应性。胃和结肠平滑肌细胞显示较弱的sGC β 1免疫反应性，粘膜肌层和血管中的平滑肌细胞也显示明显的免疫反应性。这些数据表明，ICC是从含nNOS的肠神经元释放的NO的主要靶点，并且一些NO信号被胃肠道中的FLC和平滑肌细胞接收。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Nitric oxide (NO) is a major signaling molecule in the gastrointestinal tract, and released NO inhibits muscular contraction. The actions of NO are mediated by stimulation of soluble guanylate cyclase (sGC, NO-sensitive GC) and a subsequent increase in cGMP concentration. To elucidate NO targets in the gastrointestinal musculature, we investigated the immunohistochemical localization of the beta 1 and alpha 1 sub-units of sGC and the distribution of neuronal NO synthase (nNOS)-containing nerves in the guinea-pig gastrointestinal tract. Distinct immunoreactivity for sGC beta 1 and sGC alpha 1 was observed in the interstitial cells of Cajal (ICC), fibroblast-like cells (FLC) and enteric neurons in the musculature. Double immunohistochemistry using anti-c-Kit antibody and anti-sGC beta 1 antibody revealed sGC beta 1 immunoreactivity in almost all intramuscular ICC throughout the entire gastrointestinal tract. Immunoelectron microscopy revealed that sGC beta 1-immunopositive cells possessed some of the criteria for intramuscular ICC: presence of caveolae; frequently associated with nerve bundles; and close contact with smooth muscle cells. sGC beta 1-immunopositive ICC were closely apposed to nNOS-containing nerve fibers in the muscle layers. Immunohistochemical and immunoelectron microscopical observations revealed that FLC in the musculature also showed sGC beta 1 immunoreactivity. FLC were often associated with nNOS-immunopositive nerve fibers. In the myenteric layer, almost all myenteric ganglia contained nNOS-immunopositive nerve cells and were surrounded by myenteric ICC and FLC. Myenteric ICC in the large intestine and FLC in the entire gastrointestinal tract showed sGC beta 1 immunoreactivity in the myenteric layer. Smooth muscle cells in the stomach and colon showed weak sGC beta 1 immunoreactivity, and those in the muscularis mucosae and vasculature also showed evident immunoreactivity. These data suggest that ICC are primary targets for NO released from nNOS-containing enteric neurons, and that some NO signals are received by FLC and smooth muscle cells in the gastrointestinal tract. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.