title: Heat and noxious chemical sensor, chicken TRPA1, as a target of bird repellents and identification of its structural determinants by multispecies functional comparison.
abstract: Nociceptive receptors enable animals to sense tissue-damaging stimuli, thus playing crucial roles in survival. Due to evolutionary diversification, responses of nociceptive receptors to specific stimuli can vary among species. Multispecies functional comparisons of nociceptive receptors help elucidate their evolutionary process and molecular basis for activation. The transient receptor potential ankyrin 1 (TRPA1) ion channel serves as a nociceptive receptor for chemical and thermal stimuli that is heat-activated in reptiles and frogs while potentially cold-activated in rodents. Here, we characterized channel properties of avian TRPA1 in chicken. Chicken TRPA1 was activated by noxious chemicals that also activate TRPA1 in other vertebrates. Regarding thermal sensitivity, chicken TRPA1 was activated by heat stimulation, but not cold, thus thermal sensitivity of avian TRPA1 does not coincide with rodent TRPA1, although both are homeotherms. Furthermore, in chicken sensory neurons, TRPA1 was highly coexpressed with TRPV1, another nociceptive heat and chemical receptor, similar to mammals and frogs. These results suggest that TRPA1 acted as a noxious chemical and heat receptor, and was coexpressed with TRPV1 in the ancestral terrestrial vertebrate. The acquisition of TRPV1 as a novel heat receptor in the ancestral terrestrial vertebrate is likely to have affected the functional evolution of TRPA1 regarding thermal sensitivity and led to the diversification among diverse vertebrate species. Additionally, we found for the first time that chicken TRPA1 is activated by methyl anthranilate (MA) and its structurally related chemicals used as nonlethal bird repellents. MA-induced responses were abolished by a TRPA1 antagonist in somatosensory neurons, indicating that TRPA1 acts as a MA receptor in chicken. Furthermore, TRPA1 responses to MA varied among five diverse vertebrate species. Utilizing species diversity and mutagenesis experiments, three amino acids were identified as critical residues for MA-induced activation of chicken TRPA1.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institute of Natural Sciences, Okazaki, Aichi, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Nagako
authors.initials: N
authors.lastname: Banzawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Fukuta
authors.forename: Claire T
authors.initials: CT
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohta
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001717:Birds; D002645:Chickens; D019143:Evolution, Molecular; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D059225:Nociception / Q000187:drug effects*; D009865:Oocytes / Q000378:metabolism; D010571:Pest Control; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D050916:TRPV Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000737:chemistry* / Q000378:metabolism*; D014982:Xenopus laevis; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D062367:ortho-Aminobenzoates; C038892:methyl anthranilate
keywords: bird repellents; functional evolution; heat- and chemical-sensitive channel; multispecies functional comparison; nociceptive receptor TRPA1