Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells
Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells
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DOI：
10.1210/en.2003-1728
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发表时间：
2004-05-01
期刊：
影响因子：
4.8
通讯作者：
Spindel, ER
中科院分区：
文献类型：
--
作者：
Proskocil, BJ;Sekhon, HS;Spindel, ER
乙酰胆碱（ACh）作为中枢和外周神经系统中的关键神经递质的作用是公认的。然而，ACh的作用可能更广泛，因为ACh也可以作为一种自分泌或旁分泌信号分子在各种非神经组织中发挥作用。开始建立乙酰胆碱的非神经元起源作为一种旁分泌激素在肺，我们已经检查了新生儿和成年猴支气管上皮细胞的成分参与烟碱胆碱能信号。使用免疫组化和RT-PCR，我们已经证明了在肺支气管上皮细胞（BECs）表达胆碱乙酰转移酶，囊泡乙酰胆碱转运蛋白，胆碱高亲和力转运蛋白，α 7，α 4和β 2烟碱乙酰胆碱受体（nAChR）亚基，和nAChR辅助蛋白lynx 1。共聚焦显微镜显示这些因子在上皮细胞中表达，并且与邻近的神经纤维明显不同。通过PCR产物的部分序列分析和cDNA克隆确认了RNA同一性。BEC原代培养证实了ACh的合成和分泌以及胆碱酯酶的活性。因此，ACh符合肺支气管上皮自分泌/旁分泌激素的所有标准。肺内的非神经元胆碱能信号通路为胆碱能药物提供了一个潜在的重要靶点。这一途径也可以解释尼古丁对胎儿发育的一些影响，并提供了吸烟影响肺癌生长和发育的其他机制。
The role of acetylcholine (ACh) as a key neurotransmitter in the central and peripheral nervous system is well established. However, the role of ACh may be broader because ACh may also function as an autocrine or paracrine signaling molecule in a variety of nonneuronal tissues. To begin to establish ACh of nonneuronal origin as a paracrine hormone in lung, we have examined neonatal and adult monkey bronchial epithelium for the components involved in nicotinic cholinergic signaling. Using immunohistochemistry and RT-PCR, we have demonstrated in lung bronchial epithelial cells (BECs) expression of choline acetyltransferase, the vesicular ACh transporter, the choline high-affinity transporter, alpha7, alpha4, and beta2 nicotinic ACh receptor (nAChR) subunits, and the nAChR accessory protein lynx1. Confocal microscopy demonstrates that these factors are expressed in epithelial cells and are clearly distinct from neighboring nerve fibers. Confirmation of RNA identity has been confirmed by partial sequence analysis of PCR products and by cDNA cloning. Primary culture of BECs confirms the synthesis and secretion of ACh and the activity of cholinesterases. Thus, ACh meets all the criteria for an autocrine/paracrine hormone in lung bronchial epithelium. The nonneuronal cholinergic signaling pathway in lung provides a potentially important target for cholinergic drugs. This pathway may also explain some of the effects of nicotine on fetal development and also provides additional mechanisms by which smoking affects lung cancer growth and development.