Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats
The swallowing reflex is an essential physiological reflex that allows food or liquid to pass into the esophagus from the oral cavity. Delayed triggering of this reflex is a significant health problem in patients with oropharyngeal dysphagia for which no pharmacological treatments exist. Transient r...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1149793/full |
| _version_ | 1797900474193543168 |
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| author | Mohammad Zakir Hossain Hiroshi Ando Shumpei Unno Rita Rani Roy Junichi Kitagawa |
| author_facet | Mohammad Zakir Hossain Hiroshi Ando Shumpei Unno Rita Rani Roy Junichi Kitagawa |
| author_sort | Mohammad Zakir Hossain |
| collection | DOAJ |
| description | The swallowing reflex is an essential physiological reflex that allows food or liquid to pass into the esophagus from the oral cavity. Delayed triggering of this reflex is a significant health problem in patients with oropharyngeal dysphagia for which no pharmacological treatments exist. Transient receptor potential channels have recently been discovered as potential targets to facilitate triggering of the swallowing reflex. However, the ability of transient receptor potential vanilloid 4 (TRPV4) to trigger the swallowing reflex has not been studied. Here, we demonstrate the involvement of TRPV4 in triggering the swallowing reflex in rats. TRPV4 immunoreactive nerve fibers were observed in the superior laryngeal nerve (SLN)-innervated swallowing-related regions. Retrograde tracing with fluorogold revealed localization of TRPV4 on approximately 25% of SLN-afferent neurons in the nodose–petrosal–jugular ganglionic complex. Among them, approximately 49% were large, 35% medium, and 15% small-sized SLN-afferent neurons. Topical application of a TRPV4 agonist (GSK1016790A) to the SLN-innervated regions dose-dependently facilitated triggering of the swallowing reflex, with the highest number of reflexes triggered at a concentration of 250 μM. The number of agonist-induced swallowing reflexes was significantly reduced by prior topical application of a TRPV4 antagonist. These findings indicate that TRPV4 is expressed on sensory nerves innervating the swallowing-related regions, and that its activation by an agonist can facilitate swallowing. TRPV4 is a potential pharmacological target for the management of oropharyngeal dysphagia. |
| first_indexed | 2024-04-10T08:45:33Z |
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| id | doaj.art-24fb0ae812fe4dd3af6b4e8fa501b2b4 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-10T08:45:33Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-24fb0ae812fe4dd3af6b4e8fa501b2b42023-02-22T08:05:00ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-02-011710.3389/fncel.2023.11497931149793Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in ratsMohammad Zakir Hossain0Hiroshi Ando1Shumpei Unno2Rita Rani Roy3Junichi Kitagawa4Department of Oral Physiology, School of Dentistry, Matsumoto Dental University, Shiojiri, JapanDepartment of Biology, School of Dentistry, Matsumoto Dental University, Shiojiri, JapanDepartment of Oral Physiology, School of Dentistry, Matsumoto Dental University, Shiojiri, JapanDepartment of Oral Physiology, School of Dentistry, Matsumoto Dental University, Shiojiri, JapanDepartment of Oral Physiology, School of Dentistry, Matsumoto Dental University, Shiojiri, JapanThe swallowing reflex is an essential physiological reflex that allows food or liquid to pass into the esophagus from the oral cavity. Delayed triggering of this reflex is a significant health problem in patients with oropharyngeal dysphagia for which no pharmacological treatments exist. Transient receptor potential channels have recently been discovered as potential targets to facilitate triggering of the swallowing reflex. However, the ability of transient receptor potential vanilloid 4 (TRPV4) to trigger the swallowing reflex has not been studied. Here, we demonstrate the involvement of TRPV4 in triggering the swallowing reflex in rats. TRPV4 immunoreactive nerve fibers were observed in the superior laryngeal nerve (SLN)-innervated swallowing-related regions. Retrograde tracing with fluorogold revealed localization of TRPV4 on approximately 25% of SLN-afferent neurons in the nodose–petrosal–jugular ganglionic complex. Among them, approximately 49% were large, 35% medium, and 15% small-sized SLN-afferent neurons. Topical application of a TRPV4 agonist (GSK1016790A) to the SLN-innervated regions dose-dependently facilitated triggering of the swallowing reflex, with the highest number of reflexes triggered at a concentration of 250 μM. The number of agonist-induced swallowing reflexes was significantly reduced by prior topical application of a TRPV4 antagonist. These findings indicate that TRPV4 is expressed on sensory nerves innervating the swallowing-related regions, and that its activation by an agonist can facilitate swallowing. TRPV4 is a potential pharmacological target for the management of oropharyngeal dysphagia.https://www.frontiersin.org/articles/10.3389/fncel.2023.1149793/fulltransient receptor potential vanilloid 4swallowing reflexGSK1016790Asuperior laryngeal nerve-afferentsnodose–petrosal–jugular ganglionic complex |
| spellingShingle | Mohammad Zakir Hossain Hiroshi Ando Shumpei Unno Rita Rani Roy Junichi Kitagawa Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats Frontiers in Cellular Neuroscience transient receptor potential vanilloid 4 swallowing reflex GSK1016790A superior laryngeal nerve-afferents nodose–petrosal–jugular ganglionic complex |
| title | Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| title_full | Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| title_fullStr | Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| title_full_unstemmed | Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| title_short | Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| title_sort | pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats |
| topic | transient receptor potential vanilloid 4 swallowing reflex GSK1016790A superior laryngeal nerve-afferents nodose–petrosal–jugular ganglionic complex |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1149793/full |
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