Kaji Izumi, Kaunitz Jonathan D
aGreater Los Angeles VA Healthcare System bDepartment of Medicine cDepartment of Surgery, University of California, Los Angeles, California, USA.
Curr Opin Gastroenterol. 2017 Nov;33(6):439-445. doi: 10.1097/MOG.0000000000000396.
We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa.
Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation. Some EECs and tuft cells are directly linked to sensory nerves in the subepithelial space. Vagal afferent neurons that innervate the intestinal villi express nutrient receptors, contributing to the regulation of duodenal anion secretion in response to luminal nutrients. Nutrients are also absorbed via specific epithelial transporters.
Gastric and duodenal epithelial cells are continually exposed to submolar concentrations of nutrients that activate GPCRs expressed on EECs, tuft cells, and submucosal afferent nerves and are also absorbed through specific transporters, regulating epithelial cell proliferation, gastrointestinal physiological function, and metabolism. The chemical coding and distribution of EECs and tuft cells are keys to the development of GPCR-targeted therapies.
我们报告了最近发表的有关肠道化学感应机制的知识,重点关注在肠道肠内分泌细胞(EEC)、簇状细胞以及胃十二指肠黏膜和黏膜下层传入神经中表达的营养感应G蛋白偶联受体(GPCR)。
EEC和簇状细胞的基因谱分析揭示了多种营养感应GPCR的表达。EEC和簇状细胞的密度会因旁路手术后或存在黏膜炎症时可能发生的管腔环境变化而改变。一些EEC和簇状细胞直接与上皮下间隙中的感觉神经相连。支配肠绒毛的迷走传入神经元表达营养受体,有助于调节十二指肠对管腔营养物质的阴离子分泌。营养物质也通过特定的上皮转运体被吸收。
胃和十二指肠上皮细胞持续暴露于亚摩尔浓度的营养物质中,这些营养物质激活EEC、簇状细胞和黏膜下传入神经上表达的GPCR,并通过特定转运体被吸收,从而调节上皮细胞增殖、胃肠道生理功能和新陈代谢。EEC和簇状细胞的化学编码和分布是开发GPCR靶向疗法的关键。