Del Valle-Pinero A Y, Suckow S K, Zhou Q, Perez F M, Verne G N, Caudle R M
Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Neuroscience. 2007 Jun 15;147(1):164-73. doi: 10.1016/j.neuroscience.2007.02.063. Epub 2007 May 23.
N-methyl-D-aspartate (NMDA) receptors and the expression of their different splice variants and subunits were previously characterized in the brain and spinal cord. However, knowledge on the NMDA receptor expression and function in the enteric nervous system is limited. Previous work suggested that NMDA receptors were involved in a rat model of visceral hypersensitivity. The aim of this study was to characterize the expression of the NMDA receptor NR1 splice variants and the NR2 subunit subtypes in the rat colon. We visualized the expression of NR1 protein in the rat submucosal and myenteric plexuses. The NR1 splice variants found in the colon of rats lacked the N1 and C1 cassettes and contained the C2 and C2' cassettes (NR1(000) and NR1(001)). The NR2B and NR2D subunits were also found in the rat colon. Moreover, NMDA receptors in the rat colon were heteromeric, since NR1 was co-localized with NR2B and NR2D subunits using fluorescent immunohistochemistry. The identification of the NMDA receptors in the enteric nervous system could lead to the development of drugs that selectively modulate bowel function.
N-甲基-D-天冬氨酸(NMDA)受体及其不同剪接变体和亚基的表达先前已在脑和脊髓中得到表征。然而,关于NMDA受体在肠神经系统中的表达和功能的了解有限。先前的研究表明,NMDA受体参与了内脏超敏反应的大鼠模型。本研究的目的是表征NMDA受体NR1剪接变体和NR2亚基亚型在大鼠结肠中的表达。我们观察了大鼠黏膜下和肌间神经丛中NR1蛋白的表达。在大鼠结肠中发现的NR1剪接变体缺少N1和C1盒式结构,包含C2和C2'盒式结构(NR1(000)和NR1(001))。在大鼠结肠中还发现了NR2B和NR2D亚基。此外,大鼠结肠中的NMDA受体是异聚体,因为使用荧光免疫组织化学法显示NR1与NR2B和NR2D亚基共定位。肠神经系统中NMDA受体的鉴定可能会促使开发出选择性调节肠道功能的药物。