Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. ; Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
J Neurogastroenterol Motil. 2014 Jan;20(1):41-53. doi: 10.5056/jnm.2014.20.1.41. Epub 2013 Dec 30.
BACKGROUND/AIMS: Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists. We reassessed the premise that glutamatergic signaling in the ENS recapitulates its neurotransmitter role in the CNS.
Pharmacological analysis of actions of receptor agonists and antagonists in concert with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on intracellularly-recorded electrical and synaptic behavior of ENS neurons, on stimulation of mucosal secretion by secretomotor neurons in the submucosal plexus and on muscle contractile behavior mediated by musculomotor neurons in the myenteric plexus.
Immunoreactivity for glutamate was expressed in ENS neurons. ENS neurons expressed immunoreactivity for the EAAC-1 glutamate transporter. Neither L-glutamate nor glutamatergic receptor agonists had excitatory actions on ENS neurons. Metabotropic glutamatergic receptor agonists did not directly stimulate neurogenic mucosal chloride secretion. Neither L-glutamate nor the metabotropic glutamatergic receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from either guinea pig or human small intestinal preparations.
Early discoveries, for excitatory glutamatergic neurotransmission in the CNS, inspired enthusiasm that investigation in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case.
背景/目的：消化膳食蛋白会提高小肠腔内谷氨酸的浓度，其中一些会进入肠神经系统 (ENS)。在中枢神经系统 (CNS) 中，谷氨酸是一种兴奋性神经递质。一个持续存在的观点认为，ENS 中的谷氨酸能神经生理学再现了 CNS 中的谷氨酸能功能。我们重新评估了 ENS 中的谷氨酸能信号传递再现其在 CNS 中神经递质作用的前提。
我们使用受体激动剂和拮抗剂的药理学分析与谷氨酸转运体和受体的免疫组织化学定位相结合，来评估该假说。分析集中于 ENS 神经元的细胞内记录的电和突触行为、黏膜下神经丛中的分泌运动神经元刺激黏膜分泌以及肌间神经丛中的肌肉运动神经元介导的肌肉收缩行为。
ENS 神经元表达谷氨酸的免疫反应性。ENS 神经元表达 EAAC-1 谷氨酸转运体的免疫反应性。L-谷氨酸或谷氨酸能受体激动剂对 ENS 神经元没有兴奋作用。代谢型谷氨酸能受体激动剂不能直接刺激神经源性黏膜氯离子分泌。L-谷氨酸或代谢型谷氨酸能受体激动剂，氨基环戊烷-1,3-二羧酸 (ACPD)，均未改变来自豚鼠或人小肠的肠环行或纵行肌条中自发性收缩的平均幅度。
早期在 CNS 中发现的兴奋性谷氨酸能神经传递激发了人们的热情，即 ENS 的研究将产生再现 CNS 谷氨酸能故事的发现。我们发现事实并非如此。
