Anhert-Hilger G, Stadtbäumer A, Strübing C, Scherübl H, Schultz G, Riecken E O, Wiedenmann B
Medizinische Klinik und Poliklinik, Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Gastroenterology. 1996 May;110(5):1595-604. doi: 10.1053/gast.1996.v110.pm8613067.
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.
In human pancreatic neuroendocrine tumors and corresponding mammalian cell lines, the expression of key proteins if regulated secretion were detected by immunofluorescence microscopy. Using 3H-gamma-aminobutyric acid (GABA), uptake and release by small synaptic vesicle analogues were studied.
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 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.
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.
神经内分泌细胞及其衍生的肿瘤含有储存激素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表征小突触囊泡途径。
在人胰腺神经内分泌肿瘤及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关键蛋白的表达。利用3H-γ-氨基丁酸（GABA）研究小突触囊泡类似物的摄取和释放。
从14例患者获得的肿瘤组织表达神经分泌关键蛋白，如突触小泡蛋白、 syntaxins和SNAP 25。这些蛋白也在细胞系AR42J、BON、RIN和INR中被发现。这些细胞系通过低亲和力质膜转运体特异性转运GABA，并显示出对三磷酸腺苷敏感的GABA摄取进入细胞内区室。储存的GABA在调节性胞吐作用刺激下释放。电生理分析表明，钙依赖性分泌主要由L型电压依赖性钙通道激活介导，但也由N型和可能的T型介导。
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调节性胞吐作用储存和分泌GABA以及可能的其他氨基酸递质。
