Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2010 Dec 01;9911:3609-18. doi: 10.1016/j.bpj.2010.10.014.
Show Gene links
Show Anatomy links
The Met268Pro mutation of mouse TRPA1 changes the effect of caffeine from activation to suppression.
Nagatomo K
,
Ishii H
,
Yamamoto T
,
Nakajo K
,
Kubo Y
.
???displayArticle.abstract???
The transient receptor potential A1 channel (TRPA1) is activated by various compounds, including isothiocyanates, menthol, and cinnamaldehyde. The sensitivities of the rodent and human isoforms of TRPA1 to menthol and the cysteine-attacking compound CMP1 differ, and the molecular determinants for these differences have been identified in the 5th transmembrane region (TM5) for menthol and TM6 for CMP1. We recently reported that caffeine activates mouse TRPA1 (mTRPA1) but suppresses human TRPA1 (hTRPA1). Here we aimed to identify the molecular determinant that is responsible for species-specific differences in the response to caffeine by analyzing the functional properties of various chimeras expressed in Xenopus oocytes. We initially found that the region between amino acids 231 and 287, in the distal N-terminal cytoplasmic region of mTRPA1, is critical. In a mutagenesis study of this region, we subsequently observed that introduction of a Met268Pro point mutation into mTRPA1 changed the effect of caffeine from activation to suppression. Because the region including Met-268 is different from other reported ligand-binding sites and from the EF-hand motif, these results suggest that the caffeine response is mediated by a unique mechanism, and confirm the importance of the distal N-terminal region for regulation of TRPA1 channel activity.
Al-Anzi,
Response of Drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1.
2006, Pubmed
Al-Anzi,
Response of Drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1.
2006,
Pubmed
Andersson,
Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress.
2008,
Pubmed
Bandell,
Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.
2004,
Pubmed
Bandell,
High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol.
2006,
Pubmed
Bautista,
TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
2006,
Pubmed
Chen,
Molecular determinants of species-specific activation or blockade of TRPA1 channels.
2008,
Pubmed
Chen,
TRPA1: the species difference.
2009,
Pubmed
Clapham,
International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.
2005,
Pubmed
Doerner,
Transient receptor potential channel A1 is directly gated by calcium ions.
2007,
Pubmed
Fujita,
Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels.
2007,
Pubmed
Fujita,
Intracellular alkalization causes pain sensation through activation of TRPA1 in mice.
2008,
Pubmed
Hinman,
TRP channel activation by reversible covalent modification.
2006,
Pubmed
Hu,
Zinc activates damage-sensing TRPA1 ion channels.
2009,
Pubmed
Jordt,
Molecular basis for species-specific sensitivity to "hot" chili peppers.
2002,
Pubmed
Jordt,
Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
2004,
Pubmed
Karashima,
Bimodal action of menthol on the transient receptor potential channel TRPA1.
2007,
Pubmed
Karashima,
TRPA1 acts as a cold sensor in vitro and in vivo.
2009,
Pubmed
Klionsky,
Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists.
2007,
Pubmed
Koo,
Hydroxy-alpha-sanshool activates TRPV1 and TRPA1 in sensory neurons.
2007,
Pubmed
Macpherson,
The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin.
2005,
Pubmed
Macpherson,
Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.
2007,
Pubmed
McNamara,
TRPA1 mediates formalin-induced pain.
2007,
Pubmed
Montell,
The TRP superfamily of cation channels.
2005,
Pubmed
Nagatomo,
Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels.
2008,
Pubmed
,
Xenbase
Ramsey,
An introduction to TRP channels.
2006,
Pubmed
Story,
ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.
2003,
Pubmed
Talavera,
Nicotine activates the chemosensory cation channel TRPA1.
2009,
Pubmed
Trevisani,
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
2007,
Pubmed
Venkatachalam,
TRP channels.
2007,
Pubmed
Xiao,
Identification of transmembrane domain 5 as a critical molecular determinant of menthol sensitivity in mammalian TRPA1 channels.
2008,
Pubmed
Zhang,
Transient receptor potential A1 mediates an osmotically activated ion channel.
2008,
Pubmed
Zurborg,
Direct activation of the ion channel TRPA1 by Ca2+.
2007,
Pubmed
