Filpa Viviana, Moro Elisabetta, Protasoni Marina, Crema Francesca, Frigo Gianmario, Giaroni Cristina
Department of Clinical and Experimental Medicine, University of Insubria, via H. Dunant 5, I-21100 Varese, Italy.
Department of Internal Medicine and Therapeutics, Section of Pharmacology, via Ferrata 9, I-27100 Pavia, Italy.
Neuropharmacology. 2016 Dec;111:14-33. doi: 10.1016/j.neuropharm.2016.08.024. Epub 2016 Aug 22.
Several studies have been carried out in the last 30 years in the attempt to clarify the possible role of glutamate as a neurotransmitter/neuromodulator in the gastrointestinal tract. Such effort has provided immunohistochemical, biomolecular and functional data suggesting that the entire glutamatergic neurotransmitter machinery is present in the complex circuitries of the enteric nervous system (ENS), which participates to the local coordination of gastrointestinal functions. Glutamate is also involved in the regulation of the brain-gut axis, a bi-directional connection pathway between the central nervous system (CNS) and the gut. The neurotransmitter contributes to convey information, via afferent fibers, from the gut to the brain, and to send appropriate signals, via efferent fibers, from the brain to control gut secretion and motility. In analogy with the CNS, an increasing number of studies suggest that dysregulation of the enteric glutamatergic neurotransmitter machinery may lead to gastrointestinal dysfunctions. On the whole, this research field has opened the possibility to find new potential targets for development of drugs for the treatment of gastrointestinal diseases. The present review analyzes the more recent literature on enteric glutamatergic neurotransmission both in physiological and pathological conditions, such as gastroesophageal reflux, gastric acid hypersecretory diseases, inflammatory bowel disease, irritable bowel syndrome and intestinal ischemia/reperfusion injury.
在过去30年里，人们进行了多项研究，试图阐明谷氨酸作为神经递质/神经调节剂在胃肠道中可能发挥的作用。这些研究提供了免疫组织化学、生物分子和功能数据，表明整个谷氨酸能神经递质机制存在于肠神经系统（ENS）的复杂回路中，该系统参与胃肠道功能的局部协调。谷氨酸还参与脑-肠轴的调节，脑-肠轴是中枢神经系统（CNS）与肠道之间的双向连接途径。这种神经递质通过传入纤维将信息从肠道传递到大脑，并通过传出纤维从大脑发送适当信号，以控制肠道分泌和蠕动。与中枢神经系统类似，越来越多的研究表明，肠谷氨酸能神经递质机制失调可能导致胃肠道功能障碍。总体而言，该研究领域为寻找治疗胃肠道疾病的新药开发新的潜在靶点提供了可能性。本综述分析了有关生理和病理条件下肠谷氨酸能神经传递的最新文献，这些条件包括胃食管反流、胃酸分泌过多性疾病、炎症性肠病、肠易激综合征和肠道缺血/再灌注损伤。
