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Thymol and related phenols are potent activators of the transient receptor potential channel, TRPA1
Author(s) -
Lee S. Paul,
Buber M. Tulu,
Cerne Rok,
Cortes Rosa Y.,
Bryant Robert W.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1158-c
Subject(s) - chemistry , thymol , transient receptor potential channel , menthol , camphor , capsaicin , trpv1 , ec50 , stereochemistry , pharmacology , biochemistry , food science , receptor , organic chemistry , in vitro , essential oil , medicine
Thymol is a major component of the spice thyme. It has a distinctive pungent flavor mediated by receptor mechanisms in the nose and tongue in addition to having aversive properties. Using a voltage‐sensitive fluorescent dye, we show that thymol specifically activates the human transient receptor potential channel A1 (TRPA1), EC 50 12 μM, but not other taste sensory TRP channels (TRPV1 and TRPM5). Electrophysiology measurements further demonstrated that thymol activation was concentration‐dependent, reversible, and rapidly desensitized TRPA1. A number of related phenols including 3‐tert‐butyl‐4‐hydroxyanisol (BHA), a food preservative, and propofol, an intravenous anesthetic, also selectively activated TRPA1 (EC 50 3 and 13 μM, respectively). Phenols with less bulky carbon substitutions adjacent to the phenolic group, such as 2, 6‐dimethlyphenol and 2‐methlyphenol (o‐cresol), were less potent. TRPA1‐specific siRNA inhibited thymol activation, confirming the specificity of the response. In addition, thymol activation was blocked by camphor (IC 50 200–500 μM) whereas other camphor analogs, e.g. camphorquinone, camphoric acid and limonene were TRPA1 agonists (EC 50 0.3, 2, 3 mM, respectively). Our results suggest a role of TRPA1 activation in the reported pungent and aversive properties of some of the pharmaceutically important phenols.