Zanner Robert, Gratzl Manfred, Prinz Christian
II. Medizinische Klinik, Technische Universitat Müunchen, 81675 Munchen, Germany.
Ann N Y Acad Sci. 2002 Oct;971:389-96. doi: 10.1111/j.1749-6632.2002.tb04501.x.
Enterochromaffin-like (ECL) cells are neuroendocrine cells in the gastric epithelium characterized by numerous electron-empty, histamine-containing secretory vesicles. The antral hormone gastrin is the key stimulus of histamine secretion from this cell type, thereby controling acid secretion. Following receptor binding, gastrin activates a biphasic calcium signal in ECL cells that involves activation of inositol triphosphate receptors and calcium entry across the plasma membrane. Dihydropyridines block gastrin-induced histamine secretion. However, no depolarization was observed following stimulation with gastrin. Elevation of intracellular calcium by gastrin is an important prerequisite for exocytosis. In permeabilized ECL cells, addition of calcium results in histamine release, which can be inhibited by tetanus toxin and botulinum neurotoxin A, underlining the functional importance of the synaptosome-associated protein of 25 kDa (SNAP-25) and synaptobrevin. Immunocytochemistry also confirmed the presence of these SNAP receptor (SNARE) proteins, as well as synaptophysin, synaptotagmin, and syntaxin. Following 3-6 h of incubation in isolated cells, several transcription factors are induced by gastrin, such as ERK1/2, Sp1, and CRE. Gastrin thereby directly stimulates transcription of the vesicular monoamine transporter subtype 2 (VMAT-2) and chromogranins. Gene expression of histidine decarboxylase (HDC) appears to be stimulated by a putative "gastrin-responsive" element adjacent to the HDC exon 1 gene. ECL cells thereby share several similarities with adrenal chromaffin cells and neurons, but have their own functional properties. Gastrin coordinates secretion, synthesis, and storage by activating diverging signal transducers, leading to a functional synergy in this cell type.
肠嗜铬样（ECL）细胞是胃上皮中的神经内分泌细胞，其特征是含有大量电子透明、含组胺的分泌小泡。胃窦激素胃泌素是这种细胞类型分泌组胺的关键刺激物，从而控制胃酸分泌。胃泌素与受体结合后，会在ECL细胞中激活双相钙信号，这涉及肌醇三磷酸受体的激活以及钙通过质膜的内流。二氢吡啶可阻断胃泌素诱导的组胺分泌。然而，用胃泌素刺激后未观察到去极化现象。胃泌素引起的细胞内钙升高是胞吐作用的重要前提。在通透的ECL细胞中，添加钙会导致组胺释放，破伤风毒素和肉毒杆菌神经毒素A可抑制这种释放，这突出了25 kDa突触体相关蛋白（SNAP-25）和突触小泡蛋白的功能重要性。免疫细胞化学也证实了这些SNAP受体（SNARE）蛋白以及突触素、突触结合蛋白和 syntaxin的存在。在分离的细胞中孵育3-6小时后，胃泌素会诱导几种转录因子，如ERK1/2、Sp1和CRE。胃泌素由此直接刺激囊泡单胺转运体2型（VMAT-2）和嗜铬粒蛋白的转录。组氨酸脱羧酶（HDC）的基因表达似乎受到HDC外显子1基因附近一个假定的“胃泌素反应性”元件的刺激。因此，ECL细胞与肾上腺嗜铬细胞和神经元有一些相似之处，但具有自身的功能特性。胃泌素通过激活不同的信号转导器来协调分泌、合成和储存，从而在这种细胞类型中产生功能协同作用。
