8 7. 5 uM respectively, i. e. a more than 5 fold difference. Most of the agonists used in the present study selleck catalog acti vated TAS2R4, 7, 10, 14, 39, 43 and 46 with threshold concentrations in HEK cells mostly between 3 and 300 uM, but none was selective for a single Inhibitors,Modulators,Libraries receptor subtype. The involvement of TAS2R4, 13, 39, 43 and 46 in bron chial relaxation seems rather unlikely, since concentrations Inhibitors,Modulators,Libraries of up to 1 mM denatonium and colchi cine were devoid of effect. In human bronchi, the most potent non selective agonists were chloroquine and diphenidol, followed by quinine, strychnine and caffeine. Phenanthro line induced relaxation for concentrations as low as 10 uM suggesting the in volvement of TAS2R5. Phenanthroline was at least as ef fective and potent as chloroquine to relax human bronchi.

The TAS2R14 agonists, carisoprodol and flufenamic acid, as well as the TAS2R10 agonists erythromycin and dapsone caused equipotent, similarly effective re laxations. A role for TAS2R10 has been previously sug gested in ASM by blockade of the strychnine induced calcium mobilisation Inhibitors,Modulators,Libraries by a TAS2R10 raised antibody. In contrast, the involvement of TAS2R7 is unlikely since sodium cromoglycate and malvidin Inhibitors,Modulators,Libraries 3 glucoside did not affect bronchial tone for concentrations equivalent or greater than their EC50 in HEK cells. A role for TAS2R8, 9 and 31 is also unlikely because of the inactivity of ofloxa cin and saccharin, in agreement with the low expression of these subtypes transcripts in human bronchi.

Similarly, the in volvement of receptors TAS2R19, 41, 42, 45 and 60 in the relaxation of human bronchi is unlikely since they are Inhibitors,Modulators,Libraries considered orphan receptors www.selleckchem.com/products/dorsomorphin-2hcl.html and none of the agonists of the present study is known to activate these receptor sub types. Given the absence of selective agonists for TAS2R1, 3 and 13, the involvement of these latter recep tors could not be specifically investigated and thus cannot be formally ruled out. One limitation of our study relates to the incomplete pharmacological characterization of the available TAS2R agonists. For example, it has also been suggested that chloroquine inhibits airway smooth muscle contractility by inhibiting phospholipase A2. Caffeine was found to relax airway smooth muscle by direct actin depoly merisation and quinine reportedly bypasses taste re ceptors and directly activates G proteins. Likewise, the non steroidal anti inflammatory flufenamic acid in hibits the cyclooxygenases responsible for producing pros taglandins, which are prominent mediators of bronchial tone. However, flufenamic acids agonistic prop erties towards TAS2R14 have been well characterized. Indomethacin, another potent cyclooxygenase inhibitor, was a much less potent relaxant in our model.