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Variability in P2X receptor composition in human taste nerves: implications for treatment of chronic cough

Authors :
Brigit High
Marie E. Jetté
Mei Li
Vijay R. Ramakrishnan
Matthew Clary
Jeremy Prager
Julia Draf
Thomas Hummel
Thomas E. Finger
Source :
ERJ Open Research, Vol 9, Iss 2 (2023)
Publication Year :
2023
Publisher :
European Respiratory Society, 2023.

Abstract

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.

Subjects

Subjects :
Medicine

Details

Language :
English
ISSN :
23120541
Volume :
9
Issue :
2
Database :
Directory of Open Access Journals
Journal :
ERJ Open Research
Publication Type :
Academic Journal
Accession number :
edsdoj.b2966b37d945689afe78df86bcb950
Document Type :
article
Full Text :
https://doi.org/10.1183/23120541.00007-2023