title: The involvement of TRP channels in sensory irritation: a mechanistic approach toward a better understanding of the biological effects of local irritants.
abstract: Peripheral nerves innervating the mucosae of the nose, mouth, and throat protect the organism against chemical hazards. Upon their stimulation, characteristic perceptions (e.g., stinging and burning) and various reflexes are triggered (e.g., sneezing and cough). The potency of a chemical to cause sensory irritation can be estimated by a mouse bioassay assessing the concentration-dependent decrease in the respiratory rate (50 % decrease: RD50). The involvement of the N. trigeminus and its sensory neurons in the irritant-induced decrease in respiratory rates are not well understood to date. In calcium imaging experiments, we tested which of eight different irritants (RD50 5-730 ppm) could induce responses in primary mouse trigeminal ganglion neurons. The tested irritants acetophenone, 2-ethylhexanol, hexyl isocyanate, isophorone, and trimethylcyclohexanol stimulated responses in trigeminal neurons. Most of these responses depended on functional TRPA1 or TRPV1 channels. For crotyl alcohol, 3-methyl-1-butanol, and sodium metabisulfite, no activation could be observed. 2-ethylhexanol can activate both TRPA1 and TRPV1, and at low contractions (100 µM) G protein-coupled receptors (GPCRs) seem to be involved. GPCRs might also be involved in the mediation of the responses to trimethylcyclohexanol. By using neurobiological tools, we showed that sensory irritation in vivo could be based on the direct activation of TRP channels but also on yet unknown interactions with GPCRs present in trigeminal neurons. Our results showed that the potency suggested by the RD50 values was not reflected by direct nerve-compound interaction.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. rlehmann@ifado.de.
authors.forename: Ramona
authors.initials: R
authors.lastname: Lehmann
authors.affiliation: Department of Animal Physiology, Ruhr University Bochum, Universitätsstr. 150, 44780, Bochum, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schöbel
authors.affiliation: Department of Cell Physiology, Ruhr University Bochum, Universitätsstr. 150, 44780, Bochum, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: van Thriel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007509:Irritants / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D020545:Respiratory Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D056152:Respiratory Rate / Q000187:drug effects; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000473:pathology
chemical_list: D007509:Irritants; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse
keywords: Calcium imaging; Chemosensation; Respiratory rate; TRP channels; Trigeminal neurons; Volatile organic compounds