title: Long-lasting facilitation of respiratory rhythm by treatment with TRPA1 agonist, cinnamaldehyde.
abstract: The transient receptor potential (TRP) channels are widely distributed in the central nervous system (CNS) and peripheral nervous system. We examined the effects of TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and allyl isothiocyanate) on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats [postnatal days 0-3 (P0-P3)] and in in situ-perfused preparations from juvenile rats (P11-P13). Preparations were superfused with modified Krebs solution at 25-26°C, and activity of inspiratory C4 ventral root (or phrenic nerve) was monitored. In the newborn rat, an in vitro preparation of cinnamaldehyde (0.5 mM) induced typically biphasic responses in C4 rate: an initial short increase and subsequent decrease, then a gradual recovery of rhythm during 15 min of bath application. After washout, the respiratory rhythm rate further increased, remaining 200% of control for >120 min, indicating long-lasting facilitation. Allyl isothiocyanate induced effects similar to those of cinnamaldehyde. The long-lasting facilitation of respiratory rhythm was partially antagonized by the TRPA1 antagonist HC-030031 (10 μM). We obtained similar long-lasting facilitation in an in situ-perfused reparation from P11-P13 rats. On the basis of results from transection experiments of the rostral medulla and whole-cell recordings from preinspiratory neurons in the parafacial respiratory group (pFRG), we suggest that the rostral medulla, including the pFRG, is important to the induction of long-lasting facilitation. A histochemical analysis demonstrated a wide distribution of TRPA1 channel-positive cells in the reticular formation of the medulla, including the pFRG. Our findings suggest that TRPA1 channel activation could induce long-lasting facilitation of respiratory rhythm and provide grounds for future study on the roles of TRPA1 channels in the CNS.
authors.affiliation: Department of Physiology, Showa University School of Medicine, Tokyo, Japan;
authors.forename: Mariho
authors.initials: M
authors.lastname: Tani
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan;
authors.forename: Itaru
authors.initials: I
authors.lastname: Yazawa
authors.affiliation: Division of Biology, Hyogo College of Medicine, Hyogo, Japan; and.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Physiology, Showa University School of Medicine, Tokyo, Japan; oni@med.showa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onimaru
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D003655:Decerebrate State; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017879:Isothiocyanates / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D011687:Purines / Q000494:pharmacology; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D019141:Respiratory System Agents / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D017879:Isothiocyanates; D011687:Purines; D019141:Respiratory System Agents; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D000171:Acrolein; C004471:allyl isothiocyanate; C012843:cinnamaldehyde
keywords: facilitation; respiratory rhythm; transient receptor potential ankyrin 1