gamma-aminobutyric acid secretion from pancreatic neuroendocrine cells
gamma-aminobutyric acid secretion from pancreatic neuroendocrine cells
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DOI：
10.1053/gast.1996.v110.pm8613067
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发表时间：
1996-05-01
期刊：
影响因子：
29.4
通讯作者：
Wiedenmann, B
中科院分区：
文献类型：
--
作者：
AhnertHilger, G;Stadtbaumer, A;Wiedenmann, B
背景和目标：神经内分泌细胞和由其衍生的肿瘤含有储存神经元的大致密核心囊泡和功能未知的神经元样小突触囊泡类似物。本研究的目的是详细描述小突触囊泡通路。研究方法：在人胰腺神经内分泌肿瘤和相应的哺乳动物细胞系中，通过免疫荧光显微镜检测调节分泌的关键蛋白的表达。使用H-3-γ-氨基丁酸（GABA），小突触囊泡类似物的摄取和释放进行了研究。结果：14例患者的肿瘤组织表达神经分泌的关键蛋白，如突触小泡蛋白、突触融合蛋白和SNAP 25。这些蛋白质也存在于细胞系AR 42 J、BON、RIN和INR中。该细胞系特异性地通过低亲和力质膜转运蛋白转运GABA，并显示出三磷酸腺苷敏感的GABA摄取进入细胞内室。储存的GABA在受调节的胞吐作用刺激时释放。电生理学分析表明，钙依赖性分泌介导的电压依赖性钙通道的激活主要是L型，但也的N和可能的T型。结论：神经内分泌细胞和肿瘤中的小突触囊泡类似物可以通过与神经元类似的受调节的胞吐作用储存和分泌GABA和可能的其他氨基酸递质。
Background & Aims: Neuroendocrine cells and tumors derived therefrom contain hormone-storing large dense core vesicles and neuron-like small synaptic vesicle analogues with unknown function. The aim of this study was to characterize the small synaptic vesicle pathway in detail. Methods: In human pancreatic neuroendocrine tumors and corresponding mammalian cell lines, the expression of key proteins of regulated secretion were detected by immunofluorescence microscopy. Using H-3-gamma-aminobutyric acid (GABA), uptake and release by small synaptic vesicle analogues were studied. Results: Tumor tissues obtained from 14 patients expressed key proteins of neurosecretion such as synaptobrevin, syntaxins, and SNAP 25. These proteins were also found in the cell lines AR42J, BON, RIN, and INR. The cell lines specifically transported GABA by a low-affinity plasma membrane transporter and showed an adenosine triphosphate-sensitive GABA uptake into an intracellular compartment. Stored GABA was released upon stimulation by regulated exocytosis. Electrophysiological analyses suggested that calcium-dependent secretion was mediated by activation of voltage-dependent calcium channels of mainly the L type, but also of the N and probably the T type. Conclusions: Small synaptic vesicle analogues in neuroendocrine cells and tumors can store and secrete GABA and probably other amino acid transmitters by regulated exocytosis comparable with neurons.