Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production
Bitter taste receptors (T2Rs) are G-protein-coupled receptors (GPCRs) expressed on the tongue but also in various locations throughout the body, including on motile cilia within the upper and lower airways. Within the nasal airway, T2Rs detect secreted bacterial ligands and initiate bactericidal nit...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/13/10/3392 |
| _version_ | 1797513549491208192 |
|---|---|
| author | Ryan M. Carey Nithin D. Adappa James N. Palmer Robert J. Lee |
| author_facet | Ryan M. Carey Nithin D. Adappa James N. Palmer Robert J. Lee |
| author_sort | Ryan M. Carey |
| collection | DOAJ |
| description | Bitter taste receptors (T2Rs) are G-protein-coupled receptors (GPCRs) expressed on the tongue but also in various locations throughout the body, including on motile cilia within the upper and lower airways. Within the nasal airway, T2Rs detect secreted bacterial ligands and initiate bactericidal nitric oxide (NO) responses, which also increase ciliary beat frequency (CBF) and mucociliary clearance of pathogens. Various neuropeptides, including neuropeptide tyrosine (neuropeptide Y or NPY), control physiological processes in the airway including cytokine release, fluid secretion, and ciliary beating. NPY levels and/or density of NPYergic neurons may be increased in some sinonasal diseases. We hypothesized that NPY modulates cilia-localized T2R responses in nasal epithelia. Using primary sinonasal epithelial cells cultured at air–liquid interface (ALI), we demonstrate that NPY reduces CBF through NPY2R activation of protein kinase C (PKC) and attenuates responses to T2R14 agonist apigenin. We find that NPY does not alter T2R-induced calcium elevation but does reduce T2R-stimulated NO production via a PKC-dependent process. This study extends our understanding of how T2R responses are modulated within the inflammatory environment of sinonasal diseases, which may improve our ability to effectively treat these disorders. |
| first_indexed | 2024-03-10T06:18:08Z |
| format | Article |
| id | doaj.art-5430d5c021e44e7c95d19e02cca0dae6 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T06:18:08Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-5430d5c021e44e7c95d19e02cca0dae62023-11-22T19:27:51ZengMDPI AGNutrients2072-66432021-09-011310339210.3390/nu13103392Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide ProductionRyan M. Carey0Nithin D. Adappa1James N. Palmer2Robert J. Lee3Department of Otorhinolaryngology—Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Otorhinolaryngology—Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Otorhinolaryngology—Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Otorhinolaryngology—Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USABitter taste receptors (T2Rs) are G-protein-coupled receptors (GPCRs) expressed on the tongue but also in various locations throughout the body, including on motile cilia within the upper and lower airways. Within the nasal airway, T2Rs detect secreted bacterial ligands and initiate bactericidal nitric oxide (NO) responses, which also increase ciliary beat frequency (CBF) and mucociliary clearance of pathogens. Various neuropeptides, including neuropeptide tyrosine (neuropeptide Y or NPY), control physiological processes in the airway including cytokine release, fluid secretion, and ciliary beating. NPY levels and/or density of NPYergic neurons may be increased in some sinonasal diseases. We hypothesized that NPY modulates cilia-localized T2R responses in nasal epithelia. Using primary sinonasal epithelial cells cultured at air–liquid interface (ALI), we demonstrate that NPY reduces CBF through NPY2R activation of protein kinase C (PKC) and attenuates responses to T2R14 agonist apigenin. We find that NPY does not alter T2R-induced calcium elevation but does reduce T2R-stimulated NO production via a PKC-dependent process. This study extends our understanding of how T2R responses are modulated within the inflammatory environment of sinonasal diseases, which may improve our ability to effectively treat these disorders.https://www.mdpi.com/2072-6643/13/10/3392bitter taste receptorsneuropeptide Ysinusitisnitric oxideciliainnate immunity |
| spellingShingle | Ryan M. Carey Nithin D. Adappa James N. Palmer Robert J. Lee Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production Nutrients bitter taste receptors neuropeptide Y sinusitis nitric oxide cilia innate immunity |
| title | Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production |
| title_full | Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production |
| title_fullStr | Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production |
| title_full_unstemmed | Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production |
| title_short | Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production |
| title_sort | neuropeptide y reduces nasal epithelial t2r bitter taste receptor stimulated nitric oxide production |
| topic | bitter taste receptors neuropeptide Y sinusitis nitric oxide cilia innate immunity |
| url | https://www.mdpi.com/2072-6643/13/10/3392 |
| work_keys_str_mv | AT ryanmcarey neuropeptideyreducesnasalepithelialt2rbittertastereceptorstimulatednitricoxideproduction AT nithindadappa neuropeptideyreducesnasalepithelialt2rbittertastereceptorstimulatednitricoxideproduction AT jamesnpalmer neuropeptideyreducesnasalepithelialt2rbittertastereceptorstimulatednitricoxideproduction AT robertjlee neuropeptideyreducesnasalepithelialt2rbittertastereceptorstimulatednitricoxideproduction |