title: Nasal TRPA1 mediates irritant-induced bradypnea in mice.
abstract: Transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily, exists in sensory neurons such as trigeminal neurons innervating the nasal cavity and vagal neurons innervating the trachea and the lung. Although TRPA1 has been proposed as an irritant receptor that, when stimulated, triggers bradypnea, precise locations of the receptors responsible have not been elucidated. Here, we examined the relative importance of TRPA1 located in the upper airway (nasal) and the lower airway (trachea/lungs) in urethane-anesthetized mice. To stimulate the upper and lower airways separately, two cannulas were inserted through a hole made in the trachea just caudal to the thyroid cartilage, one into the nasal cavity and the second into the lower trachea. A vapor of one of the TRPA1-agonists, allyl isothiocyanate (AITC), was introduced by placing a piece of cotton paper soaked with AITC solution into the airline. AITC decreased the respiratory frequency when applied to the upper airway (ca -30%) but not to the lower airway (ca -5%). No response was observed in TRPA1 knockout mice. Contribution of the olfactory nerve seemed minimal because olfactory bulbectomized wild-type mice showed a similar response to that of the intact mice. AITC-induced bradypnea seemed to be mediated, at least in part, by the trigeminal nerve because trigeminal ganglion neurons were activated by AITC as revealed by an increase in the phosphorylated form of extracellular signal-regulated kinase in the neurons. These data clearly show that trigeminal TRPA1 in the nasal cavity play an essential role in irritant-induced bradypnea.
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Inui
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: ChangPing
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Pauli
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.|Anesthesiology & Critical Care Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kuroki
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.|Anesthesiology & Critical Care Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Anesthesiology & Critical Care Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanmura
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kashiwadani
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, Japan kuwaki@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwaki
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D007509:Irritants / Q000008:administration & dosage*; D017879:Isothiocyanates / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009832:Olfactory Nerve / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D000074025:TRPA1 Cation Channel / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D007509:Irritants; D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate; D048052:Mitogen-Activated Protein Kinase 3
keywords: Allyl isothiocyanate; extracellular signal‐regulated kinase; olfactory nerve; trigeminal nerve; vagal nerve