TY - JOUR
T1 - Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells
AU - Robinett, Kathryn S.
AU - Koziol-White, Cynthia J.
AU - Akoluk, Arda
AU - An, Steven S.
AU - Panettieri, Reynold A.
AU - Liggett, Stephen B.
PY - 2014/4
Y1 - 2014/4
N2 - Bitter taste receptors (TAS2Rs) have recently been found to be expressed on human airway smooth muscle (HASM), and their activation results in marked relaxation. These agents have been proposed as a new class of bronchodilators in the treatment of obstructive lung diseases because they act via a different mechanism than b-agonists. The TAS2R signal transduction pathway in HASM has multiple elements that are potentially subject to regulation by inflammatory, genetic, and epigenetic mechanisms associated with asthma. To address this, expression, signaling, and physiologic functions of the three major TAS2Rs (subtypes 10, 14, and 31) on HASM were studied. Transcript expression of these TAS2Rs was not decreased inHASMcells derived from donors with asthma compared with those without asthma (n = 6 from each group). In addition, intracellular calcium ([Ca2+]i) signaling using TAS2R subtype-specific agonists (diphenhydramine, chloroquine, saccharin, and flufenamic acid) was not impaired in the cells derived from donors with asthma, nor was the response to quinine, which activates all three subtypes. HASM cell mechanics measured by magnetic twisting cytometry revealed equivalent TAS2R-mediated relaxation of methacholine-treated cells between the two groups. Human precision-cut lung slices treated with IL-13 caused a decrease in β-agonist (formoterol)-mediated relaxation of carbacholcontracted airways compared with control slices. In contrast, TAS2R-mediated relaxation was unaffected by IL-13. We conclude that TAS2R expression or function is unaffected in HASM cells derived from patients with asthma or the IL-13 inflammatory environment.
AB - Bitter taste receptors (TAS2Rs) have recently been found to be expressed on human airway smooth muscle (HASM), and their activation results in marked relaxation. These agents have been proposed as a new class of bronchodilators in the treatment of obstructive lung diseases because they act via a different mechanism than b-agonists. The TAS2R signal transduction pathway in HASM has multiple elements that are potentially subject to regulation by inflammatory, genetic, and epigenetic mechanisms associated with asthma. To address this, expression, signaling, and physiologic functions of the three major TAS2Rs (subtypes 10, 14, and 31) on HASM were studied. Transcript expression of these TAS2Rs was not decreased inHASMcells derived from donors with asthma compared with those without asthma (n = 6 from each group). In addition, intracellular calcium ([Ca2+]i) signaling using TAS2R subtype-specific agonists (diphenhydramine, chloroquine, saccharin, and flufenamic acid) was not impaired in the cells derived from donors with asthma, nor was the response to quinine, which activates all three subtypes. HASM cell mechanics measured by magnetic twisting cytometry revealed equivalent TAS2R-mediated relaxation of methacholine-treated cells between the two groups. Human precision-cut lung slices treated with IL-13 caused a decrease in β-agonist (formoterol)-mediated relaxation of carbacholcontracted airways compared with control slices. In contrast, TAS2R-mediated relaxation was unaffected by IL-13. We conclude that TAS2R expression or function is unaffected in HASM cells derived from patients with asthma or the IL-13 inflammatory environment.
KW - Asthma
KW - Bitter taste
KW - Bronchodilator
KW - Receptor
KW - β-agonist
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U2 - 10.1165/rcmb.2013-0439RC
DO - 10.1165/rcmb.2013-0439RC
M3 - Article
C2 - 24219573
AN - SCOPUS:84898727600
VL - 50
SP - 678
EP - 683
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 4
ER -