Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling
Abstract Background Epithelial solitary chemosensory cell (tuft cell) bitter taste signal transduction occurs through G protein coupled receptors and calcium-dependent signaling pathways. Type II taste cells, which utilize the same bitter taste signal transduction pathways, may also utilize cyclic a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-021-01631-0 |
| _version_ | 1818412667996471296 |
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| author | Michael A. Kohanski Lauren Brown Melissa Orr Li Hui Tan Nithin D. Adappa James N. Palmer Ronald C. Rubenstein Noam A. Cohen |
| author_facet | Michael A. Kohanski Lauren Brown Melissa Orr Li Hui Tan Nithin D. Adappa James N. Palmer Ronald C. Rubenstein Noam A. Cohen |
| author_sort | Michael A. Kohanski |
| collection | DOAJ |
| description | Abstract Background Epithelial solitary chemosensory cell (tuft cell) bitter taste signal transduction occurs through G protein coupled receptors and calcium-dependent signaling pathways. Type II taste cells, which utilize the same bitter taste signal transduction pathways, may also utilize cyclic adenosine monophosphate (cAMP) as an independent signaling messenger in addition to calcium. Methods In this work we utilized specific pharmacologic inhibitors to interrogate the short circuit current (Isc) of polarized nasal epithelial cells mounted in Ussing chambers to assess the electrophysiologic changes associated with bitter agonist (denatonium) treatment. We also assessed release of human β-defensin-2 from polarized nasal epithelial cultures following treatment with denatonium benzoate and/or potassium channel inhibitors. Results We demonstrate that the bitter taste receptor agonist, denatonium, decreases human respiratory epithelial two-pore potassium (K2P) current in polarized nasal epithelial cells mounted in Ussing chambers. Our data further suggest that this occurs via a cAMP-dependent signaling pathway. We also demonstrate that this decrease in potassium current lowers the threshold for denatonium to stimulate human β-defensin-2 release. Conclusions These data thus demonstrate that, in addition to taste transducing calcium-dependent signaling, bitter taste receptor agonists can also activate cAMP-dependent respiratory epithelial signaling pathways to modulate K2P currents. Bitter-agonist regulation of potassium currents may therefore serve as a means of rapid regional epithelial signaling, and further study of these pathways may provide new insights into regulation of mucosal ionic composition and innate mechanisms of epithelial defense. |
| first_indexed | 2024-12-14T10:50:58Z |
| format | Article |
| id | doaj.art-35148e1f60af410b803d6b6ab3bae10f |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-14T10:50:58Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-35148e1f60af410b803d6b6ab3bae10f2022-12-21T23:05:13ZengBMCRespiratory Research1465-993X2021-01-0122111010.1186/s12931-021-01631-0Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signalingMichael A. Kohanski0Lauren Brown1Melissa Orr2Li Hui Tan3Nithin D. Adappa4James N. Palmer5Ronald C. Rubenstein6Noam A. Cohen7Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania Medical Center, Perelman School of MedicineCystic Fibrosis Center, The Children’s Hospital of PhiladelphiaCystic Fibrosis Center, The Children’s Hospital of PhiladelphiaDepartment of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania Medical Center, Perelman School of MedicineDepartment of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania Medical Center, Perelman School of MedicineDepartment of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania Medical Center, Perelman School of MedicineCystic Fibrosis Center, The Children’s Hospital of PhiladelphiaDepartment of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania Medical Center, Perelman School of MedicineAbstract Background Epithelial solitary chemosensory cell (tuft cell) bitter taste signal transduction occurs through G protein coupled receptors and calcium-dependent signaling pathways. Type II taste cells, which utilize the same bitter taste signal transduction pathways, may also utilize cyclic adenosine monophosphate (cAMP) as an independent signaling messenger in addition to calcium. Methods In this work we utilized specific pharmacologic inhibitors to interrogate the short circuit current (Isc) of polarized nasal epithelial cells mounted in Ussing chambers to assess the electrophysiologic changes associated with bitter agonist (denatonium) treatment. We also assessed release of human β-defensin-2 from polarized nasal epithelial cultures following treatment with denatonium benzoate and/or potassium channel inhibitors. Results We demonstrate that the bitter taste receptor agonist, denatonium, decreases human respiratory epithelial two-pore potassium (K2P) current in polarized nasal epithelial cells mounted in Ussing chambers. Our data further suggest that this occurs via a cAMP-dependent signaling pathway. We also demonstrate that this decrease in potassium current lowers the threshold for denatonium to stimulate human β-defensin-2 release. Conclusions These data thus demonstrate that, in addition to taste transducing calcium-dependent signaling, bitter taste receptor agonists can also activate cAMP-dependent respiratory epithelial signaling pathways to modulate K2P currents. Bitter-agonist regulation of potassium currents may therefore serve as a means of rapid regional epithelial signaling, and further study of these pathways may provide new insights into regulation of mucosal ionic composition and innate mechanisms of epithelial defense.https://doi.org/10.1186/s12931-021-01631-0DenatoniumTuft cellSCCAntimicrobial peptideDefensinChronic rhinosinusitis |
| spellingShingle | Michael A. Kohanski Lauren Brown Melissa Orr Li Hui Tan Nithin D. Adappa James N. Palmer Ronald C. Rubenstein Noam A. Cohen Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling Respiratory Research Denatonium Tuft cell SCC Antimicrobial peptide Defensin Chronic rhinosinusitis |
| title | Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling |
| title_full | Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling |
| title_fullStr | Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling |
| title_full_unstemmed | Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling |
| title_short | Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling |
| title_sort | bitter taste receptor agonists regulate epithelial two pore potassium channels via camp signaling |
| topic | Denatonium Tuft cell SCC Antimicrobial peptide Defensin Chronic rhinosinusitis |
| url | https://doi.org/10.1186/s12931-021-01631-0 |
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