TRPA1 contributes to respiratory depression from tobacco aerosol.

Transient receptor potential ankyrin-1 (TRPA1) is expressed in the trigeminal nerves in the nasal cavity. It detects irritant chemicals such as formalin and acrolein, induces respiratory depression to protect against further inhalation, and elicits avoidance behavior. Although tobacco smoke contains formalin, acrolein, and other irritant chemicals, the possible contribution of TRPA1 to protection against tobacco smoke has yet to be fully understood. In this study, we compared respiratory and behavioral responses to an aerosol of tobacco smoke between TRPA1 conditional knockout mice and the controls. We also compared the effect of aerosols from the smoke of traditional standard tobacco and a recently developed heated tobacco product. As expected, respiratory depression by tobacco aerosol was observed only in the TRPA1 intact mice and was associated with increased trigeminal activation. Meanwhile, mice did not avoid or even prefer tobacco aerosol in a TRPA1-independent manner, contrary to our expectations. Repeated exposure to tobacco aerosol resulted in lung inflammation in a TRPA1-independent manner. Aerosols from a heated tobacco product showed no significant effect as in traditional tobacco smoke. These results indicate that TRPA1 contributes to acute protection from tobacco smoke by inducing respiratory depression but not to the safety of the lungs in repeated exposure. Tobacco aerosol contains attractive substances for mice. Heated tobacco product aerosol contains less TRPA1 activating substances and less inflammation evoking than traditional tobacco smoke.