RT Journal Article SR Electronic T1 Absence of P2X2 purinergic receptors in human taste bud innervation JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2575 DO 10.1183/13993003.congress-2020.2575 VO 56 IS suppl 64 A1 Thomas Finger A1 Brigit High YR 2020 UL http://erj.ersjournals.com/content/56/suppl_64/2575.abstract AB The success of P2X3 receptor antagonists in relieving cough (Smith et al 2020) suggests that local tissue release of ATP may activate P2X3 receptor-containing sensory nerve fibers innervating the airways. Clinical use of P2X3 receptor antagonists to ameliorate chronic cough is, however, accompanied by drug-induced taste-related adverse events due to off-target effects on purinoceptive nerve fibers innervating taste buds. In rodents, taste buds are innervated by nerve fibers expressing both P2X2 and P2X3 so many receptors are likely P2X2/P2X3 heteromers. Some researchers have tested antagonists selective for P2X3-homemeric receptors intending to avoid the gustatory side-effects of the previous drugs which impact both P2X3 homomers as well as heteromers (Garceau & Chauret, 2019). Since P2X subunit composition differs across species (Serrano et al. 2012), we used immunohistochemistry to investigate the innervation of taste buds in humans (to date: 5 fungiform samples, 5 circumvallate samples, and 11 laryngeal samples, from different individuals) and Rhesus monkey (2 fungiform and 2 circumvallate samples) to test whether the taste nerves in these species express both P2X2 and P2X3 as in mice. Antibodies to P2X2 and P2X3 were validated by Western blot by the manufacturer and by application to human gastric by-pass tissue known to contain both P2X2- and P2X3-expressing neurons in the submucosal plexus. In all taste bud samples from humans and monkey, P2X3+ fibers extensively innervate taste buds, but P2X2 is lacking, with the exception of 1 laryngeal sample. These findings indicate that taste buds in humans are primarily innervated by nerve fibers expressing only P2X3 homomeric receptors and not P2X2/P2X3 heteromers.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2575.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).