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Activation of TRPA1 by farnesyl thiosalicylic acid.
Mol Pharmacol. 2008 Apr; 73(4):1225-34.MP

Abstract

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 J(2), 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.

Authors+Show Affiliations

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18171730

Citation

Maher, Michael, et al. "Activation of TRPA1 By Farnesyl Thiosalicylic Acid." Molecular Pharmacology, vol. 73, no. 4, 2008, pp. 1225-34.
Maher M, Ao H, Banke T, et al. Activation of TRPA1 by farnesyl thiosalicylic acid. Mol Pharmacol. 2008;73(4):1225-34.
Maher, M., Ao, H., Banke, T., Nasser, N., Wu, N. T., Breitenbucher, J. G., Chaplan, S. R., & Wickenden, A. D. (2008). Activation of TRPA1 by farnesyl thiosalicylic acid. Molecular Pharmacology, 73(4), 1225-34. https://doi.org/10.1124/mol.107.042663
Maher M, et al. Activation of TRPA1 By Farnesyl Thiosalicylic Acid. Mol Pharmacol. 2008;73(4):1225-34. PubMed PMID: 18171730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of TRPA1 by farnesyl thiosalicylic acid. AU - Maher,Michael, AU - Ao,Hong, AU - Banke,Tue, AU - Nasser,Nadia, AU - Wu,Nyan-Tsz, AU - Breitenbucher,J Guy, AU - Chaplan,Sandra R, AU - Wickenden,Alan D, Y1 - 2008/01/02/ PY - 2008/1/4/pubmed PY - 2008/4/4/medline PY - 2008/1/4/entrez SP - 1225 EP - 34 JF - Molecular pharmacology JO - Mol Pharmacol VL - 73 IS - 4 N2 - 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 J(2), 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. SN - 1521-0111 UR - https://www.unboundmedicine.com/medline/citation/18171730/Activation_of_TRPA1_by_farnesyl_thiosalicylic_acid_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=18171730 DB - PRIME DP - Unbound Medicine ER -