Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine
Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine
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DOI：
10.1007/s004410100410
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发表时间：
2001-09
影响因子：
3.6
通讯作者：
H. Salmhofer;W. Neuhuber;P. Ruth;A. Huber;M. Russwurm;H. Allescher
中科院分区：
文献类型：
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作者：
H. Salmhofer;W. Neuhuber;P. Ruth;A. Huber;M. Russwurm;H. Allescher
一氧化氮（NO）信号通路是肠神经系统中主要的非肾上腺素-非胆碱能传递机制。我们的目的是通过间接免疫荧光定位大鼠小肠中的神经元型一氧化氮合酶（nNOS）、可溶性鸟苷酸环化酶（sGC）和cgmp依赖性激酶I型（cGK-I）。肌丛神经元及静脉曲张神经纤维均可见nNOS染色，主要分布于环状肌层。神经激肽-1 （NK-1）受体和c-kit阳性的细胞（Cajal间质细胞，ICC）在深肌丛（DMP）未表现出nNOS反应性，但其直接邻近有nNOS阳性的神经纤维。肌神经节周围扁平细胞（神经节周围细胞，PGC）、DMP的ICC、平滑肌细胞（SMC）和分散在圆形肌层的血管周围细胞中可见sGC。在PGC（可能是ICC）、DMP的ICC、最内环肌层和纵肌层的SMC中发现大量cGK-I免疫反应性，但在外环肌层中发现较少。弱cgk - 1染色出现在肌肠丛和粘膜下丛的神经细胞中。综上所述，NO信号通路的关键酶存在差异分布：nNOS仅在神经元中出现，sGC和cGK-I主要存在于ICC中，表明神经元的NO释放、ICC的激活和连续的平滑肌放松。DMP的ICC似乎是神经释放NO的主要目标。
The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic transmitter mechanism in the enteric nervous system. Our aim was to localize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was found in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in cells perivascularly scattered throughout the circular muscle layer. cGK-I immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less intensively in the outer circular layer. Weak cGK-I staining occurred in nerve cells within the myenteric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a sequence of neuronal NO release, activation of ICC, and consecutive smooth muscle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.