TRPA1

TRPA1 is an ion channel expressed primarily in sensory neurons of the trigeminal nerve, not in taste buds of the tongue, that senses pungent stinging sensation. Oleocanthal, contained in olive oil, activates this channel in cultured cells expressing human TRPA1 at a concentration with an EC50 of approximately 2.8 micromolar, while other receptors including TRPV1, TRPV2, TRPV4, and TRPM8 were not activated. Trigeminal neurons from TRPA1-knockout mice did not respond to oleocanthal, and when blockers were used, the response in normal mice was also abolished, confirming that this pungent sensation is mediated through TRPA1.

In the same study examining human oral and nasal tissues, TRPA1-positive cells were found abundantly in pharyngeal tissue (an average of 80 cells per 0.12 square millimeter) but were rarely seen in taste-bud tissue of the tongue (an average of 0 cells per 0.05 square millimeter). This anatomical distribution bias is proposed as an anatomical basis for the observation that oleocanthal-induced pungency is localized to the throat rather than the tongue. Additionally, experiments using mutant variants showed that this activation does not depend on the typical covalent binding mechanism involving specific cysteine (a sulfur-containing amino acid) that TRPA1 possesses.

Pungent compounds derived from garlic, such as allicin and diallyl disulfide, have also been confirmed to activate cultured cells engineered to carry TRPA1 and sensory nerve cells. TRPA1 is a protein that functions as a sensor converting pungent stimuli into nerve signals, and these cell-based experiments do not measure the intensity of pungency actually perceived by people when eating or its safety. TRPA1 is not a receptor for bitterness itself but should be distinguished as a separate sensory system conveying stinging and pungency.