, Volume 3, Issue 3-4, pp 190-199
Date: 28 Sep 2010

Four Irritating Odorants Target the Trigeminal Chemoreceptor TRPA1

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Abstract

The trigeminal nerve responds to a variety of nociceptive stimuli, including many chemicals that activate the olfactory system at lower concentrations. However, the mechanisms by which specific odorants activate the trigeminal nerve are largely undetermined. We used an integrative approach to determine whether TRPA1 channels were the target of eight olfactory stimuli known to activate the trigeminal nerve. In a mammalian cell line stably expressing the human TRPA1 channel, we observed significant increases in intracellular calcium levels upon application of α-terpineol, amyl acetate, benzaldehyde, and toluene. Notably, these responses were greatly reduced when these chemicals were applied in conjunction with the TRPA1 inhibitor HC-030031. To determine whether TRPA1 is required for detecting these odorants as irritants in vivo, we evaluated physiological and behavioral responses to these stimuli in mice lacking the TRPA1 channel. A decline in respiration was seen in wild-type but not TRPA1 knockout mice upon exposure to α-terpineol, benzaldehyde, and toluene. Furthermore, we observed either attenuated or absent avoidance behaviors in TRPA1 knockout mice compared to wild-type mice when exposed to α-terpineol, amyl acetate, and benzaldehyde. Our results show that TRPA1 is a molecular target for four different odorants—α-terpineol, amyl acetate, benzaldehyde, and toluene. Additionally, this study suggests that TRPA1 is required for detection of α-terpineol, benzaldehyde, and toluene as trigeminal irritants. However, TRPA1 is likely only one of multiple trigeminal receptors detecting amyl acetate.