Interstitial cells of Cajal are functionally innervated by excitatory motor neurones in the murine intestine
Interstitial cells of Cajal are functionally innervated by excitatory motor neurones in the murine intestine
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DOI：
10.1113/jphysiol.2003.058792
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发表时间：
2004-04-15
影响因子：
5.5
通讯作者：
Sanders, KM
中科院分区：
文献类型：
--
作者：
Iino, S;Ward, SA;Sanders, KM
最近的研究表明，肌内Cajal间质细胞（ICC）是胃神经传递的优先靶点。肠运动神经元的终末也与小肠和结肠中的ICC形成紧密的突触样接触，但对这些细胞在神经传递中的作用知之甚少。ICC在小肠深肌丛（ICC-Ⅲ）表达神经激肽I受体（NK 1 R），并内化这些受体在响应外源性P物质。我们使用NK 1 R内化作为ICC-Ⅲ在小鼠小肠的功能性神经支配的测定。在基础状态下，NK 1 R样免疫反应（NK 1 R-LI）主要见于ICC-cells（计数519个细胞，阳性率100%）和肌间神经元。ICC-神经纤维与含P物质的神经纤维紧密贴壁。在检查的338个ICC-DMP中，65%与至少一种P物质阳性神经纤维密切相关，32%与至少两种相关，2%与两种以上神经纤维相关，1%与无神经纤维相关。在电场刺激（EFS，10 Hz; 1 min）后，NK 1 R-LI在超过80%的ICC-TNM中内化，而在EFS前为10%。在肌间ICC或平滑肌细胞对神经刺激的反应中未观察到NK 1 R的内化。NK 1 R-LI的内化被特异性NK 1受体拮抗剂WIN 62577（1 μ m）和河豚毒素（0.3 μ m）阻断，表明内化是由神经释放的神经激肽刺激受体引起的。这些数据表明，ICC-β是肠运动神经元释放的神经激肽的主要靶点。
Recent studies have demonstrated that intramuscular interstitial cells of Cajal (ICC) are preferential targets for neurotransmission in the stomach. Terminals of enteric motor neurones also form tight, synaptic-like contacts with ICC in the small intestine and colon, but little is known about the role of these cells in neurotransmission. ICC at the deep muscular plexus (ICC-DMP) of the small intestine express neurokinin I receptors (NK1R) and internalize these receptors in response to exogenous substance P. We used NK1R internalization as an assay of functional innervation of ICC-DMP in the murine small intestine. Under basal conditions NK1R-like immunoreactivity (NK1R-LI) was mainly observed in ICC-DMP (519 cells counted, 100% were positive) and myenteric neurones. ICC-DMP were closely apposed to substance P-containing nerve fibres. Of 338 ICC-DMP examined, 65% were closely associated with at least one substance P-positive nerve fibre, 32% were associated with at least two, 2% were associated with more than two nerve fibres and 1% with none. After electrical field stimulation (EFS, 10 Hz; 1 min) NK1R-LI was internalized in more than 80% of ICC-DMP, as compared to 10% of cells before EFS. Internalization of NK1R was not observed in myenteric ICC or smooth muscle cells in response to nerve stimulation. Internalization of NK1R-LI was blocked by the specific NK1 receptor antagonist WIN 62577 (1 mum) and by tetrodotoxin (0.3 mum), suggesting that internalization resulted from stimulation of receptors with neurally released neurokinins. These data suggest that ICC-DMP are primary targets for neurokinins released from enteric motor neurones in the intestine.