title: The expression and relaxant effect of bitter taste receptors in human bronchi.
abstract: BACKGROUND
  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.
  
  
  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
  We 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.
  
  
  CONCLUSIONS
  The TAS2Rs may constitute a new therapeutic target in chronic obstructive lung diseases such as asthma.
authors.affiliation: Laboratoire de Pharmacologie Respiratoire UPRES EA220, Hôpital Foch, 11 rue Guillaume Lenoir, F-92150 Suresnes, Paris, France. s.grassindelyle@hopital-foch.org.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Grassin-Delyle
authors.forename: Charlotte
authors.initials: C
authors.lastname: Abrial
authors.forename: Sarah
authors.initials: S
authors.lastname: Fayad-Kobeissi
authors.forename: Marion
authors.initials: M
authors.lastname: Brollo
authors.forename: Christophe
authors.initials: C
authors.lastname: Faisy
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Alvarez
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Naline
authors.forename: Philippe
authors.initials: P
authors.lastname: Devillier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D013649:Taste / Q000502:physiology*
chemical_list: D001993:Bronchodilator Agents; D010880:Piperidines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C568609:TAS2R1 protein, human; D002110:Caffeine; D002738:Chloroquine; D013331:Strychnine; C004858:diphenidol