Abstract
Agonists for taste sensing-type 2 receptors (TAS2Rs) relax human and rodent airways, possibly by inhibition of bronchoconstrictor-induced Ca2+. Our previous studies however suggested that the TAS2R agonists chloroquine and noscapine used different pathways to cause relaxations. We tested this hypothesis by characterising the influence of chloroquine and noscapine on Ca2+ signalling in human airway smooth muscle cells (hASM) and relaxations of human bronchi, respectively.
Human small bronchi (diameter <1 mm) were isolated from fresh surgically removed lung tissue and kept in culture for 2 days. Relaxations were studied in tissue baths after histamine pre-contraction (1 μM), and intracellular Ca2+ fluxes were measured in cultured hASM cells using Fluo-4.
Chloroquine and noscapine (1-100 μM) induced maximal relaxations of 96±4% and 56±1% respectively (n=4). In hASM cells, chloroquine caused concentration-dependent inhibitions of histamine-induced Ca2+ release, whereas noscapine had less effect on this Ca2+ release (Figure, one representative experiment of n=3).
The bitter tastants comprise a novel class of bronchodilators affecting several distinct pathways. Thus, for the first time, we show that chloroquine and noscapine had different effects on calcium fluxes in hASM cells, despite both bitter compounds being able to relax small human bronchi.
- © 2014 ERS