Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction
Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction
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DOI：
10.1007/s00424-014-1551-x
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发表时间：
2015-04-01
影响因子：
4.5
通讯作者：
Tazaki, Masakazu
中科院分区：
文献类型：
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作者：
Shibukawa, Yoshiyuki;Sato, Masaki;Tazaki, Masakazu
当各种刺激作用于暴露的牙本质表面时，会引起疼痛。然而，牙本质疼痛的机制仍不清楚。我们研究了直接机械刺激成牙细胞后成牙细胞和三叉神经节神经元之间的细胞间信号转导。机械刺激单个成牙细胞通过激活机械敏感瞬时受体电位（TRP）通道TRPV1、TRPV2、TRPV4和TRPA1，而不是TRPM8通道，增加细胞内游离钙浓度（[Ca2+](i)）。在成牙细胞和TG神经元的共培养中，不仅在机械刺激的成牙细胞中，而且在邻近的成牙细胞和TG神经元中也观察到[Ca2+](i)的增加。在没有细胞外Ca2+和机械敏感TRP通道拮抗剂存在的情况下，这些[Ca2+](i)的增加被消除。pannexin-1 （atp可渗透通道）抑制剂和atp降解酶可消除邻近成牙细胞和TG神经元中[Ca2+](i)的增加，但在受刺激的成牙细胞中没有。g蛋白偶联P2Y核苷酸受体拮抗剂也抑制[Ca2+]的增加(i)。离子性ATP （P2X(3)）受体拮抗剂抑制邻近TG神经元中[Ca2+](i)的增加，但在受刺激的或邻近的成牙细胞中没有。在单个成牙细胞的机械刺激过程中，连接蛋白43阻断剂对任何细胞中观察到的[Ca2+](i)反应没有任何影响。这些结果表明，在TRP通道激活的情况下，机械刺激的成牙细胞通过pannexin-1释放ATP，将信号传递给TG神经元上的P2X(3)受体。我们认为成牙细胞是一种感觉受体细胞，成牙细胞释放的ATP在牙本质疼痛的感觉传导过程中作为一种神经递质发挥作用。
Various stimuli induce pain when applied to the surface of exposed dentin. However, the mechanisms underlying dentinal pain remain unclear. We investigated intercellular signal transduction between odontoblasts and trigeminal ganglion (TG) neurons following direct mechanical stimulation of odontoblasts. Mechanical stimulation of single odontoblasts increased the intracellular free calcium concentration ([Ca2+](i)) by activating the mechanosensitive-transient receptor potential (TRP) channels TRPV1, TRPV2, TRPV4, and TRPA1, but not TRPM8 channels. In cocultures of odontoblasts and TG neurons, increases in [Ca2+](i) were observed not only in mechanically stimulated odontoblasts, but also in neighboring odontoblasts and TG neurons. These increases in [Ca2+](i) were abolished in the absence of extracellular Ca2+ and in the presence of mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel) inhibitor and ATP-degrading enzyme abolished the increases in [Ca2+](i) in neighboring odontoblasts and TG neurons, but not in the stimulated odontoblasts. G-protein-coupled P2Y nucleotide receptor antagonists also inhibited the increases in [Ca2+](i). An ionotropic ATP (P2X(3)) receptor antagonist inhibited the increase in [Ca2+](i) in neighboring TG neurons, but not in stimulated or neighboring odontoblasts. During mechanical stimulation of single odontoblasts, a connexin-43 blocker did not have any effects on the [Ca2+](i) responses observed in any of the cells. These results indicate that ATP, released from mechanically stimulated odontoblasts via pannexin-1 in response to TRP channel activation, transmits a signal to P2X(3) receptors on TG neurons. We suggest that odontoblasts are sensory receptor cells and that ATP released from odontoblasts functions as a neurotransmitter in the sensory transduction sequence for dentinal pain.