| 研究実績の概要 |
In this study, we investigate the involvement of TRPA1 and TRPV4 in initiating the swallowing reflex. Our observations reveal that TRPA1 predominantly localizes on small to medium-diameter neurons, whereas TRPV4 primarily localizes on large to medium-diameter neurons. Furthermore, our investigation demonstrates that the topical administration of chemical agonists targeting TRPA1, such as allyl isothiocyanate (AITC), or TRPV4, such as GSK1016790A, in swallowing-related regions, leads to a dose-dependent facilitation of the swallowing reflex. Notably, the pre-application of antagonists for TRPA1 or TRPV4 significantly mitigates the AITC or GSK1016790A-induced swallowing reflex, respectively. Moreover, we explored the impact of temperature modulation on the triggering of reflexes. Cold AITC application briefly reduces the on-site temperature to below 17 °C, the temperature threshold for TRPA1 activation, without affecting reflex triggering. However, prolonged exposure to cold AITC or application of iced AITC paradoxically delays or prevents AITC-induced reflexes by maintaining the on-site temperature below the activation threshold for TRPA1. Interestingly, pre-application of the TRPA1 antagonist does not alter the threshold for punctate mechanical stimuli-induced reflex or the frequency of low-force or high-force continuous mechanical pressure stimuli-induced reflexes. These findings underscore the potential of targeting TRPA1 and TRPV4 to develop therapeutics to enhance swallowing function.
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