title: Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction.
abstract: 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 ([Ca(2+)]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 [Ca(2+)]i were observed not only in mechanically stimulated odontoblasts, but also in neighboring odontoblasts and TG neurons. These increases in [Ca(2+)]i were abolished in the absence of extracellular Ca(2+) and in the presence of mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel) inhibitor and ATP-degrading enzyme abolished the increases in [Ca(2+)]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 [Ca(2+)]i. An ionotropic ATP (P2X3) receptor antagonist inhibited the increase in [Ca(2+)]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 [Ca(2+)]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 P2X3 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.
authors.affiliation: Department of Physiology, Tokyo Dental College, Tokyo, 101-0061, Japan, yshibuka@tdc.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shibukawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.forename: Maki
authors.initials: M
authors.lastname: Kimura
authors.forename: Ubaidus
authors.initials: U
authors.lastname: Sobhan
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shimada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Aya
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Soya
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kuroda
authors.forename: Akira
authors.initials: A
authors.lastname: Katakura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tazaki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D005260:Female; D008297:Male; D040542:Mechanotransduction, Cellular; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009804:Odontoblasts / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; D058470:Receptors, Purinergic P2Y; D050916:TRPV Cation Channels; C479936:pannexin 1, rat; D000255:Adenosine Triphosphate; D002118:Calcium