MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on January 2, 2008; DOI: 10.1124/mol.107.042663

0026-895X/08/7304-1225-1234$20.00
Mol Pharmacol 73:1225-1234, 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.107.042663v1
73/4/1225    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maher, M.
Right arrow Articles by Wickenden, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maher, M.
Right arrow Articles by Wickenden, A. D.

Activation of TRPA1 by Farnesyl Thiosalicylic Acid

Michael Maher, Hong Ao, Tue Banke, Nadia Nasser, Nyan-Tsz Wu, J. Guy Breitenbucher, Sandra R. Chaplan, and Alan D. Wickenden

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., San Diego, California

The nonselective cation channel TRPA1 (ANKTM1, p120) is a potential mediator of pain, and selective pharmacological modulation of this channel may be analgesic. Although several TRPA1 activators exist, these tend to be either reactive or of low potency and/or selectivity. The aim of the present study, therefore, was to identify novel TRPA1 agonists. Using a combination of calcium fluorescent assays and whole-cell electrophysiology, we discovered several compounds that possess potent, selective TRPA1-activating activity, including several lipid compounds (farnesyl thiosalicylic acid, farnesyl thioacetic acid, 15-deoxy-{Delta}12,14-prostaglandin J2, and 5,8,11,14-eicosatetraynoic acid), and two marketed drugs: disulfiram (Antabuse; a compound used in the treatment of alcohol abuse) and the antifungal agent chlordantoin. Farnesyl thiosalicylic acid activates the channel in excised patches and in the absence of calcium. Furthermore, using a quadruple TRPA1 mutant, we show that the mechanism of action of farnesyl thiosalicylic acid differs from that of the reactive electrophilic reagent allylisothiocyanate. As a TRPA1 agonist with a potentially novel mechanism of action, farnesyl thiosalicylic acid may be useful in the study of TRPA1 channels.

Received October 15, 2007; accepted December 31, 2007

Address correspondence to: Dr. Alan D. Wickenden, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121. E-mail: awickend{at}prdus.jnj.com




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
B. Xiao, A. E. Dubin, B. Bursulaya, V. Viswanath, T. J. Jegla, and A. Patapoutian
Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels
J. Neurosci., September 24, 2008; 28(39): 9640 - 9651.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
T. E. Taylor-Clark, M. A. McAlexander, C. Nassenstein, S. A. Sheardown, S. Wilson, J. Thornton, M. J. Carr, and B. J. Undem
Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal
J. Physiol., July 15, 2008; 586(14): 3447 - 3459.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2008 by the American Society for Pharmacology and Experimental Therapeutics