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Transient receptor potential cation channel, subfamily A, member 1
Identifiers
Symbols TRPA1; ANKTM1
External IDs OMIM604775 MGI3522699 HomoloGene7189 IUPHAR: TRPA1 GeneCards: TRPA1 Gene
RNA expression pattern
PBB GE TRPA1 208349 at tn.png
PBB GE TRPA1 217590 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8989 277328
Ensembl ENSG00000104321 ENSMUSG00000032769
UniProt O75762 Q0VBN5
RefSeq (mRNA) NM_007332 NM_177781
RefSeq (protein) NP_015628 NP_808449
Location (UCSC) Chr 8:
73.1 - 73.15 Mb
Chr 1:
14.86 - 14.9 Mb
PubMed search [1] [2]

Transient receptor potential cation channel, subfamily A, member 1, also known as TRPA1, is a protein which in humans is encoded by the TRPA1 (and in other species by the Trpa1) gene.[1][2]

Contents

Function

TRPA1 is a member of the transient receptor potential channel family.[2] TRPA1, contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical stress sensor.[3] The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control.[4]

Recent studies indicate that TRPA1 is activated by a number reactive compounds (allyl isothiocyanate, cinnamaldehyde, farnesyl thiosalicylic acid, Nicotine and its structural analogues [Sherkheli MA, 2008],<http://www-brs.ub.ruhr-uni-bochum.de/netahtml/HSS/Diss/SherkheliMAzhar/Zusammenfassung.pdf> formalin, hydrogen peroxide, 4-hydroxynonenal, and acrolein) and considered as a 'chemosensor' in the body.[5] TRPA1 is considered as an attractive pain target based on the fact that TRPA1 knockout mice showed near complete attenuation of formalin-induced pain behaviors.[6][7] TRPA1 antagonists are effective in blocking pain behaviors induced by inflammation (complete Freund's adjuvant and formalin)

Although it is not firmly confirmed whether noxious cold sensation is mediated by TRPA1 in vivo, several recent studies clearly demonstrated cold activation of TRPA1 channels in vitro.[8][9]

Clinical significance

In 2008 it was observed that caffeine suppresses activity of human TRPA1, but it was found that mouse Trpa1 channels expressed in sensory neurons cause an aversion to drinking caffeine-containing water, suggesting they mediate the perception of caffeine.[10]

TRPA1 has also been implicated in causing the skin irritation experienced by some smokers who are trying to quit by using nicotine replacement therapies such as inhalers, sprays or patches.[11]

References

  1. ^ Jaquemar D, Schenker T, Trueb B (March 1999). "An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts". J. Biol. Chem. 274 (11): 7325–33. doi:10.1074/jbc.274.11.7325. PMID 10066796.  
  2. ^ a b Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.  
  3. ^ García-Añoveros J, Nagata K (2007). "TRPA1". Handb Exp Pharmacol (179): 347–62. doi:10.1007/978-3-540-34891-7_21. PMID 17217068.  
  4. ^ "Entrez Gene: TRPA1 transient receptor potential cation channel, subfamily A, member 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8989.  
  5. ^ Tai C, Zhu S, Zhou N (January 2008). "TRPA1: the central molecule for chemical sensing in pain pathway?". J. Neurosci. 28 (5): 1019–21. doi:10.1523/JNEUROSCI.5237-07.2008. PMID 18234879.  
  6. ^ McNamara CR, Mandel-Brehm J, Bautista DM, et al. (August 2007). "TRPA1 mediates formalin-induced pain". Proc. Natl. Acad. Sci. U.S.A. 104 (33): 13525–30. doi:10.1073/pnas.0705924104. PMID 17686976.  
  7. ^ McMahon SB, Wood JN (March 2006). "Increasingly irritable and close to tears: TRPA1 in inflammatory pain". Cell 124 (6): 1123–5. doi:10.1016/j.cell.2006.03.006. PMID 16564004.  
  8. ^ Sawada Y, Hosokawa H, Hori A, Matsumura K, Kobayashi S (July 2007). "Cold sensitivity of recombinant TRPA1 channels". Brain Res. 1160: 39–46. doi:10.1016/j.brainres.2007.05.047. PMID 17588549.  
  9. ^ Klionsky L, Tamir R, Gao B, et al. (2007). "Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists". Mol Pain 3: 39. doi:10.1186/1744-8069-3-39. PMID 18086308.  
  10. ^ Nagatomo K, Kubo Y (November 2008). "Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels". Proc. Natl. Acad. Sci. U.S.A.. doi:10.1073/pnas.0809769105. PMID 18988737.  
  11. ^ Talavera K, Gees M, Karashima Y, et al. (September 2009). "Nicotine activates the chemosensory cation channel TRPA1". Nature Neuroscience. doi:10.1038/nn.2379.  

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