Abstract
BackgroundBitter-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 sought to identify and characterize the TAS2Rs expressed in isolated human bronchi and the subtypes involved in relaxation.MethodsHuman 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.ResultsWe detected the expression of TAS2R transcripts in human bronchi. The non-selective agonists chloroquine, quinine, caffeine, strychnine and diphenidol produced a bronchial relaxation as effective and potent as theophylline but much less potent than formoterol and isoproterenol. Denatonium, saccharin and colchicine did not produce relaxation. Receptor expression analysis together with the use of selective agonists suggest a predominant role for TAS2R5, 10 and 14 in bitter taste agonist-induced relaxation. The mechanism of relaxation was independent of the signalling pathways modulated by conventional bronchodilators and may be partly explained by the inhibition of phosphatidylinositol-3-kinases.ConclusionsThe TAS2Rs may constitute a new therapeutic target in chronic obstructive lung diseases such as asthma.
Highlights
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
Drugs and chemicals The TAS2R agonists chloroquine diphosphate, quinine hydrochloride dihydrate, saccharin sodium hydrate, denatonium benzoate, 1,10-phenanthroline hydrochloride monohydrate, caffeine, colchicine, ofloxacin, malvidin-3glucoside, strychnine hemisulphate, erythromycin, dapsone, carisoprodol, flufenamic acid and sodium cromoglycate were obtained from Sigma-Aldrich (Saint Quentin Fallavier, France) and diphenidol hydrochloride was provided by TCI Europe (Zwijndrecht, Belgium)
Transcripts of genes coding for bitter taste receptors were identified in the bronchi of all patients, except those of TAS2R9, 43 and 46 found in bronchi from 8/9, 9/14 and 8/9 patients only
Summary
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 sought to identify and characterize the TAS2Rs expressed in isolated human bronchi and the subtypes involved in relaxation. Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are inflammatory diseases characterized by airway obstruction and airflow limitation. The current cornerstone of bronchodilators is β2-adrenoreceptor agonists, but several issues were raised such as tachyphylaxis or long-term safety. The development of novel therapies would be desirable, even more with therapies acting on both the inflammatory and obstructive intracellular domain is coupled to gustducin, an heterotrimeric G-protein (consisting of α, β and γ subunits) that is characteristic of taste reception [6]. The β/γ subunits are able to activate phospholipase Cβ2 (PLCβ2), leading to the generation of inositol triphosphate and the release of intracellular calcium [7,8]
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