2023 Fiscal Year Annual Research Report
Elucidating Novel Therapeutic Targets for Oropharyngeal Dysphagia: Focusing on TRPA1 and TRPV4 Channels
| Project/Area Number |
20K09898
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安藤 宏 松本歯科大学, 歯学部, 准教授 (30312094)
北川 純一 松本歯科大学, 歯学部, 教授 (50373006)
海野 俊平 松本歯科大学, 歯学部, 講師 (80418920)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | Swallowing Reflex / TRPA1 / TRPV4 |
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| Outline of Annual Research Achievements |
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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