Intercellular signal communication among odontoblasts and trigeminal ganglion neurons via glutamate
Intercellular signal communication among odontoblasts and trigeminal ganglion neurons via glutamate
复制标题
DOI：
10.1016/j.ceca.2016.07.003
复制
发表时间：
2016-11-01
期刊：
影响因子：
4
通讯作者：
Shibukawa, Y.
中科院分区：
文献类型：
--
作者：
Nishiyama, A.;Sato, M.;Shibukawa, Y.
对牙本质暴露表面的各种刺激可引起牙本质小管内流体动力的变化，从而引起牙本质疼痛。最近的证据表明，成牙细胞中的机械传感器通道，如瞬时受体电位通道，接受这些水动力并触发向牙髓神经元释放ATP，从而产生牙本质疼痛。然而，最近的一项研究表明，成牙细胞也表达谷氨酸受体（GluRs）。这表明牙髓组织细胞具有释放谷氨酸的能力，谷氨酸作为一种功能性细胞间介质，建立成牙细胞间和成牙细胞-三叉神经节（TG）神经元信号交流。为了研究细胞间的信号交流，我们对成牙细胞施加机械刺激，并测量细胞内游离Ca2+浓度（[Ca2+](i)）。在细胞外Ca2+存在的机械刺激期间，我们观察到短暂的[Ca2+](i)增加，不仅在单一刺激的成牙细胞中，而且在相邻的成牙细胞中。在没有细胞外Ca2+的情况下，我们无法观察到这些反应。[Ca2+](i)在单个成牙细胞机械刺激过程中邻近成牙细胞的增加被代谢性谷氨酸受体（mGluRs）拮抗剂和谷氨酸渗透性阴离子通道抑制。在成牙细胞-TG神经元共培养中，我们观察到受刺激的成牙细胞和TG神经元中[Ca2+](i)的增加，这是对单个成牙细胞直接机械刺激的反应。mGluRs拮抗剂抑制了邻近TG神经元中[Ca2+](i)的增加。mGluRs拮抗剂也抑制了受刺激的成牙细胞中[Ca2+](i)的增加。我们进一步证实成牙细胞表达I、II和III组mGluRs。然而，在机械刺激的成牙细胞附近，无论有无细胞外Mg2+，我们都没有记录到成牙细胞引起的电流，这表明n -甲基-d-天冬氨酸受体不参与成牙细胞间的信号交流。结果表明，机械刺激的成牙细胞能够通过谷氨酸渗透性阴离子通道将谷氨酸释放到细胞外空间。释放的谷氨酸以自分泌/旁分泌的方式激活成牙细胞上的mGluRs，形成成牙细胞间的通信，通过成牙细胞-成牙细胞信号通信驱动牙本质形成。谷氨酸和mGluRs也介导成牙髓细胞和牙髓神经元之间的神经传递，调节牙本质敏感性的感觉信号传递。(C) 2016 Elsevier Ltd.版权所有。
Various stimuli to the exposed surface of dentin induce changes in the hydrodynamic force inside the dentinal tubules resulting in dentinal pain. Recent evidences indicate that mechano-sensor channels, such as the transient receptor potential channels, in odontoblasts receive these hydrodynamic forces and trigger the release of ATP to the pulpal neurons, to generate dentinal pain. A recent study, however, has shown that odontoblasts also express glutamate receptors (GluRs). This implies that cells in the dental pulp tissue have the ability to release glutamate, which acts as a functional intercellular mediator to establish inter-odontoblast and odontoblast-trigeminal ganglion (TG) neuron signal communication. To investigate the intercellular signal communication, we applied mechanical stimulation to odontoblasts and measured the intracellular free Ca2+ concentration ([Ca2+](i)). During mechanical stimulation in the presence of extracellular Ca2+, we observed a transient [Ca2+](i) increase not only in single stimulated odontoblasts, but also in adjacent odontoblasts. We could not observe these responses in the absence of extracellular Ca2+. [Ca2+](i) increases in the neighboring odontoblasts during mechanical stimulation of single odontoblasts were inhibited by antagonists of metabotropic glutamate receptors (mGluRs) as well as glutamate-permeable anion channels. In the odontoblast-TG neuron coculture, we observed an increase in [Ca2+](i) in the stimulated odontoblasts and TG neurons, in response to direct mechanical stimulation of single odontoblasts. These [Ca2+](i) increases in the neighboring TG neurons were inhibited by antagonists for mGluRs. The [Ca2+](i) increases in the stimulated odontoblasts were also inhibited by mGluRs antagonists. We further confirmed that the odontoblasts express group I, II, and III mGluRs. However, we could not record any currents evoked from odontoblasts near the mechanically stimulated odontoblast, with or without extracellular Mg2+, indicating that N-methyl-d-aspartic acid receptor does not contribute to inter-odontoblast signal communication. The results suggest that a mechanically stimulated odontoblast is capable of releasing glutamate into the extracellular space via glutamate-permeable anion channels. The released glutamate activates mGluRs on the odontoblasts in an autocrine/paracrine manner, forming an inter-odontoblasts communication, which drives dentin formation via odontoblast-odontoblast signal communication. Glutamate and mGluRs also mediate neurotransmission between the odontoblasts and neurons in the dental pulp to modulate sensory signal transmission for dentinal sensitivity. (C) 2016 Elsevier Ltd. All rights reserved.