MolPharm xPharm- The Comprehensive Pharmacology Reference

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


     

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

This Article
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


Received for publication October 16, 2007.
Revised December 28, 2007.
Accepted for publication December 31, 2007.

Activation of TRPA1 by farnesyl thiosalicylic acid

Michael Maher 1, Hong Ao 1, Tue Banke 1, Nadia Nasser 1, Nyan-Tsz Wu 1, J Guy Breitenbucher 1, Sandra R Chaplan 1, Alan D Wickenden 1*

1 Johnson & Johnson PRD, L.L.C

* Address correspondence to: E-mail: awickend{at}prdus.jnj.com

Abstract

The non-selective cation channel TRPA1 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 anti-fungal agent, chlordantoin. Farnesyl thiosalicylic acid activates the channel in excised patches and in the absence of calcium. Furthermore, using a quadruple TRPA1 mutant (TRPA1-M4), 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.


Key words: Capsaicin/vanilloid, Ion channel regulation, Func. analysis receptor/ion channel mutants


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] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

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