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Biphasic modulation by mGlu5 receptors of TRPV1-mediated intracellular calcium elevation in sensory neurons contributes to heat sensitivity.

AbstractBACKGROUND 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 mGlu5 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 TRPV1 channels, were examined in cultured dorsal root ganglion neurons from mice.
KEY RESULTS:
Activation of mGlu5 receptors in hind paw transiently increased, then decreased, the response to noxious heat. In sensory neurons, activation of mGlu5 receptors potentiated TRPV1-mediated intracellular calcium elevation, while terminating activation of mGlu5 receptors depressed it. TRPV1-induced currents were potentiated by activation of mGlu5 receptors under voltage clamp conditions and these disappeared after washout. However, voltage-gated calcium currents were inhibited by the mGlu5 receptor agonist, even after washout.
CONCLUSIONS AND IMPLICATIONS:
These results suggest that, in sensory neurons, mGlu5 receptors biphasically modulate TRPV1-mediated intracellular calcium response via transient potentiation of TRPV1 channel-induced currents and persistent inhibition of voltage-gated calcium currents, contributing to heat hyper- and hypoalgesia.
AuthorsT Masuoka, T Nakamura, M Kudo, J Yoshida, Y Takaoka, N Kato, T Ishibashi, N Imaizumi, M Nishio
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 172 Issue 4 Pg. 1020-33 (Feb 2015) ISSN: 1476-5381 [Electronic] England
PMID25297838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 The British Pharmacological Society.
Chemical References
  • Calcium Channels
  • Grm5 protein, mouse
  • Receptor, Metabotropic Glutamate 5
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Quisqualic Acid
  • Capsaicin
  • Calcium
Topics
  • Animals
  • Calcium (metabolism)
  • Calcium Channels (physiology)
  • Capsaicin (pharmacology)
  • Cells, Cultured
  • Ganglia, Spinal (cytology)
  • Hot Temperature
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Quisqualic Acid (pharmacology)
  • Receptor, Metabotropic Glutamate 5 (agonists, metabolism)
  • Sensory Receptor Cells (drug effects, metabolism, physiology)
  • Somatosensory Disorders (metabolism)
  • TRPV Cation Channels (metabolism, physiology)

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