Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough
Background Antagonists to the P2X purinergic receptors on airway sensory nerves relieve refractory or unexplained chronic cough (RCC/UCC) but can evoke unwanted dysgeusias because the gustatory nerves innervating taste buds express this same family of receptors. However, the subunit composition of t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2023-04-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/9/2/00007-2023.full |
| _version_ | 1797809396954169344 |
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| author | Brigit High Marie E. Jetté Mei Li Vijay R. Ramakrishnan Matthew Clary Jeremy Prager Julia Draf Thomas Hummel Thomas E. Finger |
| author_facet | Brigit High Marie E. Jetté Mei Li Vijay R. Ramakrishnan Matthew Clary Jeremy Prager Julia Draf Thomas Hummel Thomas E. Finger |
| author_sort | Brigit High |
| collection | DOAJ |
| description | Background
Antagonists to the P2X purinergic receptors on airway sensory nerves relieve refractory or unexplained chronic cough (RCC/UCC) but can evoke unwanted dysgeusias because the gustatory nerves innervating taste buds express this same family of receptors. However, the subunit composition of the P2X receptors in these systems may differ, with implications for pharmacological intervention of RCC/UCC. In most species, the extrapulmonary airway nerves involved in cough predominantly express P2X3 subunits that form homotrimeric P2X3 receptors. In contrast, most sensory nerves innervating taste buds in mice express both P2X2 and P2X3 subunits, so the majority of receptors in that system are likely P2X2/P2X3 heteromers.
Methods
Since neural P2X subunit composition can differ across species, we used immunohistochemistry to test whether taste nerves in humans and rhesus macaque monkeys express both P2X2 and P2X3 as in mice.
Results
In taste bud samples of fungiform papillae and larynx from humans and monkeys, all taste bud samples exhibited P2X3+ nerve fibres, but the majority lacked substantial P2X2+. Of the 35 human subjects, only four (one laryngeal and three fungiform) showed strong P2X2 immunoreactivity in taste nerves; none of the rhesus monkey samples showed immunoreactivity for P2X2.
Conclusions
These findings suggest that for most humans, unlike mice, taste buds are innervated by nerve fibres predominantly expressing only P2X3 homomeric receptors and not P2X2/P2X3 heteromers. Thus, antagonists specific for P2X3 homomeric receptors might not be spared from affecting taste function in RCC/UCC patients. |
| first_indexed | 2024-03-13T06:52:03Z |
| format | Article |
| id | doaj.art-ceb2966b37d945689afe78df86bcb950 |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-03-13T06:52:03Z |
| publishDate | 2023-04-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-ceb2966b37d945689afe78df86bcb9502023-06-07T13:31:08ZengEuropean Respiratory SocietyERJ Open Research2312-05412023-04-019210.1183/23120541.00007-202300007-2023Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic coughBrigit High0Marie E. Jetté1Mei Li2Vijay R. Ramakrishnan3Matthew Clary4Jeremy Prager5Julia Draf6Thomas Hummel7Thomas E. Finger8 Department of Cell and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO, USA Department of Otolaryngology – Head and Neck Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Department of Cell and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO, USA Department of Otolaryngology – Head and Neck Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Department of Otolaryngology – Head and Neck Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Pediatric Otolaryngology, Children's Hospital Colorado, Aurora, CO, USA Smell and Taste Clinic, Department of Otorhinolaryngology, Technical University of Dresden, Dresden, Germany Smell and Taste Clinic, Department of Otorhinolaryngology, Technical University of Dresden, Dresden, Germany Department of Cell and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO, USA Background Antagonists to the P2X purinergic receptors on airway sensory nerves relieve refractory or unexplained chronic cough (RCC/UCC) but can evoke unwanted dysgeusias because the gustatory nerves innervating taste buds express this same family of receptors. However, the subunit composition of the P2X receptors in these systems may differ, with implications for pharmacological intervention of RCC/UCC. In most species, the extrapulmonary airway nerves involved in cough predominantly express P2X3 subunits that form homotrimeric P2X3 receptors. In contrast, most sensory nerves innervating taste buds in mice express both P2X2 and P2X3 subunits, so the majority of receptors in that system are likely P2X2/P2X3 heteromers. Methods Since neural P2X subunit composition can differ across species, we used immunohistochemistry to test whether taste nerves in humans and rhesus macaque monkeys express both P2X2 and P2X3 as in mice. Results In taste bud samples of fungiform papillae and larynx from humans and monkeys, all taste bud samples exhibited P2X3+ nerve fibres, but the majority lacked substantial P2X2+. Of the 35 human subjects, only four (one laryngeal and three fungiform) showed strong P2X2 immunoreactivity in taste nerves; none of the rhesus monkey samples showed immunoreactivity for P2X2. Conclusions These findings suggest that for most humans, unlike mice, taste buds are innervated by nerve fibres predominantly expressing only P2X3 homomeric receptors and not P2X2/P2X3 heteromers. Thus, antagonists specific for P2X3 homomeric receptors might not be spared from affecting taste function in RCC/UCC patients.http://openres.ersjournals.com/content/9/2/00007-2023.full |
| spellingShingle | Brigit High Marie E. Jetté Mei Li Vijay R. Ramakrishnan Matthew Clary Jeremy Prager Julia Draf Thomas Hummel Thomas E. Finger Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough ERJ Open Research |
| title | Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough |
| title_full | Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough |
| title_fullStr | Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough |
| title_full_unstemmed | Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough |
| title_short | Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough |
| title_sort | variability in p2x receptor composition in human taste nerves implications for treatment of chronic cough |
| url | http://openres.ersjournals.com/content/9/2/00007-2023.full |
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