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Biphasic modulation by m G lu 5 receptors of TRPV 1‐mediated intracellular calcium elevation in sensory neurons contributes to heat sensitivity
Author(s) -
Masuoka T,
Nakamura T,
Kudo M,
Yoshida J,
Takaoka Y,
Kato N,
Ishibashi T,
Imaizumi N,
Nishio M
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12962
Subject(s) - trpv , metabotropic receptor , chemistry , metabotropic glutamate receptor , ionotropic effect , dorsal root ganglion , receptor , calcium in biology , agonist , calcium , endocrinology , biophysics , glutamate receptor , medicine , transient receptor potential channel , microbiology and biotechnology , neuroscience , biochemistry , biology , trpv1 , sensory system , organic chemistry
Background and Purpose Elevation of glutamate, an excitatory amino acid, during inflammation and injury plays a crucial role in the reception and transmission of sensory information via ionotropic and metabotropic receptors. This study aimed to investigate the mechanisms underlying the biphasic effects of metabotropic glutamate m G lu 5 receptor activation on responses to noxious heat. Experimental Approach We assessed the effects of intraplantar quisqualate, a non‐selective glutamate receptor agonist, on heat and mechanical pain behaviours in mice. In addition, the effects of quisqualate on the intracellular calcium response and on membrane currents mediated by TRPV 1 channels, were examined in cultured dorsal root ganglion neurons from mice. Key Results Activation of m G lu 5 receptors in hind paw transiently increased, then decreased, the response to noxious heat. In sensory neurons, activation of m G lu 5 receptors potentiated TRPV 1‐mediated intracellular calcium elevation, while terminating activation of m G lu 5 receptors depressed it. TRPV 1‐induced currents were potentiated by activation of m G lu 5 receptors under voltage clamp conditions and these disappeared after washout. However, voltage‐gated calcium currents were inhibited by the m G lu 5 receptor agonist, even after washout. Conclusions and Implications These results suggest that, in sensory neurons, m G lu 5 receptors biphasically modulate TRPV 1‐mediated intracellular calcium response via transient potentiation of TRPV 1 channel‐induced currents and persistent inhibition of voltage‐gated calcium currents, contributing to heat hyper‐ and hypoalgesia.