Effects of bitter taste receptor agonists on the contractility of human bronchi In the first set of experiments, we used non selective TAS2R agonists to cover the widest possible range of receptors. Chloroquine, quinine, caffeine, strychnine and dipheni dol elicited marked, concentration dependent relaxation of human bronchi. The maximum effect was significantly greater Brefeldin A than the weak, spontaneous relaxation over time observed with control bronchi. As shown in Table 2, the Emax values for TAS2R agonists were close to those observed with B2?adrenorecep tor agonists isoproterenol and formoterol and with theophylline. The pD2 values of the TAS2R Inhibitors,Modulators,Libraries agonists ranged from 4. 6 0. 4 and 3. 7 0. 3 . these were close to that of theophylline but much lower than the pD2 values of formoterol and isoproterenol.

In contrast, the Emax values for other TAS2R agonists did not differ significant from controls. We also investigated the influence of bronchi diameter on the relaxation to Inhibitors,Modulators,Libraries bitter agonists. Chloroquine and phenanthroline relax with the same efficacy and po tency bronchi Inhibitors,Modulators,Libraries with diameter smaller than 1 mm and larger than 5 mm. Characterization of receptor subtypes involved in the relaxant response The receptor expression results and the above mentioned effects of certain TAS2R agonists suggested the involve ment of TAS2R7, 10 and 14 in the relaxation of human bronchi. This hypothesis was further investigated with the use of relatively selective agonists. The Inhibitors,Modulators,Libraries involvement of TAS2R5 was also probed with phenanthroline. in addition to being selective for this receptor, phenanthroline is the only TAS2R5 agonist to have been described to date.

The selective agonists of TAS2R5, TAS2R10 and TAS2R14 induced the relaxation of human bronchi, whereas the TAS2R7 agonists cromo glycate and malvidin 3 glucoside were ineffective up to 10 mM and 30 uM respectively. The potency was similar for the TAS2R5, 10 and ?14 agonists, with Reversibility Inhibitors,Modulators,Libraries of the relaxation When bronchial segments were washed three times with Krebs Henseleit solution after exposure to the highest concentration of a TAS2R agonist, the tension reverted Table 2 Maximum relaxation and potency observed with non selective TAS2R agonists and reference relaxing agents on human bronchi to its baseline value. Moreover, when 3 mM acetylcho line was applied to the preparations immediately after the wash, a contractile response greater than that ob tained with 10 uM histamine mostly was observed and was close to maximum contraction obtained with 3 mM acetylcholine in control experiments. Recovery of baseline tone and contractibility with acetylcholine were observed after exposure to all the TAS2R agonists tested in this study.