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The roles of TRPV1, TRPA1 and TRPM8 channels in chemical and thermal sensitivity of the mouse oral mucosa
Author(s) -
Kichko Tatjana I.,
Neuhuber Winfried,
Kobal Gerd,
Reeh Peter W.
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13799
Subject(s) - transient receptor potential channel , trpv1 , trpv , chemistry , trpm8 , calcitonin gene related peptide , capsaicin , capsazepine , pharmacology , trpv4 , receptor , biochemistry , biophysics , neuropeptide , biology
Spices in food and beverages and compounds in tobacco smoke interact with sensory irritant receptors of the transient receptor potential ( TRP ) cation channel family. TRPV 1 (vanilloid type 1), TRPA 1 (ankyrin 1) and TRPM 8 (melastatin 8) not only elicit action potential signaling through trigeminal nerves, eventually evoking pungent or cooling sensations, but by their calcium conductance they also stimulate the release of calcitonin gene‐related peptide ( CGRP ). This is measured as an index of neuronal activation to elucidate the chemo‐ and thermosensory transduction in the isolated mouse buccal mucosa of wild types and pertinent knockouts. We found that the lipophilic capsaicin, mustard oil and menthol effectively get access to the nerve endings below the multilayered squamous epithelium, while cigarette smoke and its gaseous phase were weakly effective releasing CGRP . The hydrophilic nicotine was ineffective unless applied unprotonated in alkaline ( pH 9) solution, activating TRPA 1 and TRPV 1. Also, mustard oil activated both these irritant receptors in millimolar but only TRPA 1 in micromolar concentrations; in combination (1 m m ) with heat (45 °C), it showed supraadditive, that is heat sensitizing, effects in TRPV 1 and TRPA 1 knockouts, suggesting action on an unknown heat‐activated channel and mustard oil receptor. Menthol caused little CGRP release by itself, but in subliminal concentration (2 m m ), it enabled a robust cold response that was absent in TRPM 8 −/− but retained in TRPA 1 −/− and strongly reduced by TRPM 8 inhibitors. In conclusion, all three relevant irritant receptors are functionally expressed in the oral mucosa and play their specific roles in inducing neurogenic inflammation and sensitization to heat and cold.