Lambrecht Nils W G, Yakubov Iskandar, Zer Cindy, Sachs George
Department of Pathology, David Geffen School of Medicine, University of California Los Angeles, California, USA.
Physiol Genomics. 2006 Mar 13;25(1):153-65. doi: 10.1152/physiolgenomics.00271.2005. Epub 2006 Jan 10.
The gastric entero-chromaffin-like (ECL) cell plays a key regulatory role in peripheral regulation of acid secretion due to the release of histamine that stimulates acid secretion by the parietal cell. Studies in intact animals, gastric glands, and isolated cells after short-term culture have shown expression of stimulatory CCK2 and PAC1 and inhibitory SST2 and Gal1 receptors as well as histidine decarboxylase. However, the pattern of its gene expression as a neuroendocrine cell has not been explored. Comparison of gene expression by 95% pure ECL cells obtained by density gradient, elutriation, and fluorescence-assisted cell sorting with isolates of the intact fundic gastric epithelium (i.e., "subtractive hybridization") identified a variety of additional expressed gene families characteristic of this neuroendocrine cell. These include genes 1) involved in neuropeptide synthesis and secretory vesicle exocytosis, 2) involved in control of inflammation, 3) implicated in healing of the epithelium, 4) encoding inhibitory Gi protein-coupled receptors, 5) playing a role in neuroendocrine regulation of food intake, and 6) encoding proteins likely involved in maintenance of circadian rhythm, in addition to the ECL cell-specific genes histidine decarboxylase and monoamine transporter. Particularly, the inhibitory apelin receptor gene, APJ, was highly expressed in the ECL cell preparation. Because parietal cells express apelin, immunohistochemical and functional studies showed that there is an inhibitory feed back loop between the parietal and ECL cell during gastrin stimulation, providing evidence for a novel pathway of downregulation of acid secretion due to interaction between these two cell types.
胃肠嗜铬样（ECL）细胞在胃酸分泌的外周调节中起关键调节作用，因为它释放的组胺可刺激壁细胞分泌胃酸。对完整动物、胃腺以及短期培养后的分离细胞的研究表明，存在刺激性CCK2和PAC1受体以及抑制性SST2和Gal1受体的表达，同时也有组氨酸脱羧酶的表达。然而，作为一种神经内分泌细胞，其基因表达模式尚未得到探索。通过密度梯度、淘洗和荧光辅助细胞分选获得的95%纯度的ECL细胞与完整胃底胃上皮细胞分离物（即“消减杂交”）的基因表达比较，确定了该神经内分泌细胞的多种其他特征性表达基因家族。这些基因包括：1）参与神经肽合成和分泌囊泡胞吐作用的基因；2）参与炎症控制的基因；3）与上皮愈合有关的基因；4）编码抑制性Gi蛋白偶联受体的基因；5）在食物摄入的神经内分泌调节中起作用的基因；6）编码可能参与维持昼夜节律的蛋白质的基因，此外还有ECL细胞特异性基因组氨酸脱羧酶和单胺转运体。特别是，抑制性apelin受体基因APJ在ECL细胞制剂中高度表达。由于壁细胞表达apelin，免疫组织化学和功能研究表明，在胃泌素刺激期间，壁细胞和ECL细胞之间存在抑制性反馈回路，这为这两种细胞类型相互作用导致胃酸分泌下调的新途径提供了证据。
