Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5.
Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5.
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DOI：
10.1053/j.gastro.2009.02.070
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发表时间：
2009-08
期刊：
影响因子：
29.4
通讯作者：
Mosinger B
中科院分区：
文献类型：
--
作者：
Kokrashvili Z;Rodriguez D;Yevshayeva V;Zhou H;Margolskee RF;Mosinger B
肠内分泌细胞是哺乳动物内分泌细胞中最大和最多样化的群体，包括肠粘膜中的许多不同细胞类型，其产生、储存和分泌调节肠道生理学的许多方面的小分子、肽和/或较大蛋白质。肠粘膜中不含分泌颗粒的不典型内分泌细胞，如刷状细胞或小窝细胞，目前知之甚少。我们研究了这些肠内分泌细胞在十二指肠，产生几种肽，包括内源性阿片类物质，也表达Trpm 5阳离子通道的子集。我们通过免疫组织化学和ELISA分析从Trpm5启动子表达绿色荧光蛋白的转基因小鼠以及野生型和Trpm5缺失小鼠的肠组织，研究了Trpm5和其他分子的表达模式。我们描述了小鼠十二指肠中的一种肠内分泌细胞，其通过Trpm 5的存在来定义，其不包含典型的分泌颗粒，但在靠近肠腔的顶端隔室中表达内源性阿片类物质（β-内啡肽和甲硫氨酸脑啡肽）和尿鸟苷素。在小鼠十二指肠中存在共表达β-内啡肽、甲硫氨酸脑啡肽、尿鸟苷肽和Trpm 5的孤立性化学感受细胞。这些细胞可能会分泌生物活性肽进入肠腔，以响应饮食因素;阿片肽的释放需要Trpm 5离子通道。
Enteroendocrine cells, the largest and most diverse population of mammalian endocrine cells, comprise a number of different cell types in the gut mucosa that produce, store, and secrete small molecules, peptides and/or larger proteins that regulate many aspects of gut physiology. Little is known about less-typical endocrine cells in the intestinal mucosa that do not contain secretory granules, such as brush or caveolated cells. We studied a subset of these enteroendocrine cells in duodenum that produce several peptides, including endogenous opioids, and that also express the Trpm5 cation channel. We studied expression patterns of Trpm5 and other molecules by immunohistochemical and ELISA analyses of intestinal tissues from transgenic mice that express green fluorescent protein from theTrpm5 promoter, as well as wild-type and Trpm5-null mice. We describe a type of enteroendocrine cell in mouse duodenum that is defined by the presence of the Trpm5, that does not contain typical secretory granules, yet expresses endogenous opioids (β-endorphin and Met-enkephalin) and uroguanylin in apical compartments close to the lumen of the gut. Solitary chemosensory cells that co-express β-endorphin, Met-enkephalin, uroguanylin and Trpm5 exist in mouse duodenum. These cells are likely to secrete the bioactive peptides into the intestinal lumen in response to dietary factors; release of the opioid peptides requires the Trpm5 ion channel.
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