title: Intercellular signal communication among odontoblasts and trigeminal ganglion neurons via glutamate.
abstract: 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+]iincrease not only in single stimulated odontoblasts, but also in adjacent odontoblasts. We could not observe these responses in the absence of extracellular Ca2+. [Ca2+]iincreases 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+]iin the stimulated odontoblasts and TG neurons, in response to direct mechanical stimulation of single odontoblasts. These [Ca2+]iincreases in the neighboring TG neurons were inhibited by antagonists for mGluRs. The [Ca2+]iincreases 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.
authors.affiliation: Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo 101-0061, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Physiology, Tokyo Dental College, Tokyo 101-0061, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Physiology, Tokyo Dental College, Tokyo 101-0061, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo 101-0061, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Katakura
authors.affiliation: Department of Physiology, Tokyo Dental College, Tokyo 101-0061, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tazaki
authors.affiliation: Department of Physiology, Tokyo Dental College, Tokyo 101-0061, Japan. Electronic address: yshibuka@tdc.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Shibukawa
mesh_terms: D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism*; D009804:Odontoblasts / Q000378:metabolism*; D015398:Signal Transduction; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid
keywords: Dental pain; Dental pulp; Glutamate receptor; Mechanosensitive channels; Odontoblast; Transient receptor potential channel