The pore-domain of TRPA1 mediates the inhibitory effect of the antagonist 6-methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole.

ABSTRACT: The transient receptor potential ion channel TRPA1 confers the ability to detect tissue damaging chemicals to sensory neurons and as a result mediates chemical nociception in vivo. Mouse TRPA1 is activated by electrophilic compounds such as mustard-oil and several physical stimuli such as cold temperature. Due to its sensory function inhibition of TRPA1 activity might provide an effective treatment against chronic and inflammatory pain. Therefore, TRPA1 has become a target for the development of analgesic drugs. 6-Methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole (Compound 31) has been identified by a chemical screen and lead optimization as an inhibitor of chemical activation of TRPA1. However, the structures or domains of TRPA1 that mediate the inhibitory effect of Compound 31 are unknown

SUBMITTER: Moldenhauer H 

PROVIDER: S-EPMC4152324 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature