RT Journal Article
SR Electronic
T1 Bitter taste receptors are expressed and induce relaxation of human bronchi
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1584
VO 42
IS Suppl 57
A1 Stanislas Grassin-Delyle
A1 Charlotte Abrial
A1 Sarah Taleb-Fayad
A1 Marion Brollo
A1 Emmanuel Naline
A1 Philippe Devillier
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P1584.abstract
AB Introduction: Bitter-taste receptors (TAS2Rs) have recently been involved in the relaxation of mouse and guinea pig airways, and increased expression of TAS2Rs was shown in blood leucocytes from asthmatic children. We addressed the expression and relaxant effect of TAS2Rs in human bronchi.Methods: Human bronchi were isolated from resected lungs and TAS2R transcripts were assessed with RT-qPCR. Relaxation to TAS2R agonists was tested in organ bath in the presence or absence of pharmacological modulators of the signalling pathways involved in bronchial relaxation.Results: The non-selective agonists chloroquine, quinine, caffeine, strychnine and diphenidol produced a concentration-dependant relaxation, with a maximal effect equivalent to about 90% of the relaxation observed with 3 mM theophylline. pD2 values were between 3.7 and 4.6, similar to that of theophylline but 3- to 5-fold less than that with formoterol and isoproterenol. Denatonium, saccharin and colchicine did not produce relaxation. Receptor expression analysis together with the use of most selective agonists suggested a predominant role for TAS2R5, 10 and 14 in the bitter taste agonist-induced relaxation. In contrast to the non-selective agonist chloroquine, the relaxation to the selective TAS2R5 agonist chloroquine was in part dependent from an intact epithelium. Bitter taste agonist-induced relaxation was independent from the intracellular signalling pathways modulated by conventional bronchodilators.Conclusion: The stimulation of TAS2Rs expressed in human bronchi induces a marked relaxation. Bitter taste receptors may become a target for the pharmacological management of obstructive lung diseases.