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Additive Effects of Odor and Bitter Taste Receptors with β2-Adrenergic Receptors on Human Airway Smooth Muscle Function
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A1213 - Additive Effects of Odor and Bitter Taste Receptors with β2-Adrenergic Receptors on Human Airway Smooth Muscle Function
Author Block: J. Huang1, D. Firer2, N. M. Bexiga3, R. A. Panettieri4, S. B. Liggett5, S. S. An1; 1Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, United States, 2Department of Bioengineering, University of Maryland, College Park, MD, United States, 3Pharmaceutical Biochemistry Technology Department, University of Sao Paulo, Sao Paulo, Brazil, 4Institute for Translational Medicine and Science, Rutgers University, New Brunswick, NJ, United States, 5Personalized Medicine and Genomicx, University of South Florida Morsani College of Medicine, Tampa, FL, United States.
Rationale: We have previously identified ‘sensory’ G protein-coupled receptors (GPCRs) of the olfactory receptor (OR) family and the bitter taste receptor (TAS2R) family expressed on human airway smooth muscle (ASM) cells and demonstrated different airway physiologic functions for both. The goal of this study was to determine the possible crosstalk between these receptor classes with β2-adrenergic receptors (β2ARs) that are commonly utilized for the treatment of bronchospasm in asthma.
Methods: We used magnetic twisting cytometry (MTC) to measure dynamic changes in single-cell contractility in cultured primary human airway smooth muscle cells (N = 3 non-asthmatic cell lines). Cognate OR, TAS2R, and β2AR ligands consisting of an odorant (nerol; 500uM), a bitter tastant (chloroquine; 500uM), and a β-agonist (isoproterenol; 1uM) were applied alone or co-applied after histamine treatment. To investigate potential downstream pathway interactions, cells were treated with β2AR or TAS2R pathway inhibitors for 5 mins prior to treatment with nerol.
Results: The combination of nerol and chloroquine consistently augmented ASM cell relaxation compared to that of nerol or chloroquine alone. In two of the three cell lines, the combination of nerol and isoproterenol increased the magnitude of cell relaxation compared to nerol or isoproterenol alone. In looking at potential crosstalk between the signaling pathways, nerol-induced relaxation was not ablated by several TAS2R pathway inhibitors, nor β2AR pathway inhibitors, suggesting that these receptors may be acting through independent pathways to promote an additive effect of cell relaxation.
Conclusions: In this study, we showed an additive effect of ligands for odor, bitter taste, and β2 adrenergic receptors in magnifying human ASM cell relaxation compared to what each ligand could achieve alone. Therefore, sensory GPCRs show promise in being targets for both individual and combination therapies for asthma treatment.
Author Block: J. Huang1, D. Firer2, N. M. Bexiga3, R. A. Panettieri4, S. B. Liggett5, S. S. An1; 1Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, United States, 2Department of Bioengineering, University of Maryland, College Park, MD, United States, 3Pharmaceutical Biochemistry Technology Department, University of Sao Paulo, Sao Paulo, Brazil, 4Institute for Translational Medicine and Science, Rutgers University, New Brunswick, NJ, United States, 5Personalized Medicine and Genomicx, University of South Florida Morsani College of Medicine, Tampa, FL, United States.
Rationale: We have previously identified ‘sensory’ G protein-coupled receptors (GPCRs) of the olfactory receptor (OR) family and the bitter taste receptor (TAS2R) family expressed on human airway smooth muscle (ASM) cells and demonstrated different airway physiologic functions for both. The goal of this study was to determine the possible crosstalk between these receptor classes with β2-adrenergic receptors (β2ARs) that are commonly utilized for the treatment of bronchospasm in asthma.
Methods: We used magnetic twisting cytometry (MTC) to measure dynamic changes in single-cell contractility in cultured primary human airway smooth muscle cells (N = 3 non-asthmatic cell lines). Cognate OR, TAS2R, and β2AR ligands consisting of an odorant (nerol; 500uM), a bitter tastant (chloroquine; 500uM), and a β-agonist (isoproterenol; 1uM) were applied alone or co-applied after histamine treatment. To investigate potential downstream pathway interactions, cells were treated with β2AR or TAS2R pathway inhibitors for 5 mins prior to treatment with nerol.
Results: The combination of nerol and chloroquine consistently augmented ASM cell relaxation compared to that of nerol or chloroquine alone. In two of the three cell lines, the combination of nerol and isoproterenol increased the magnitude of cell relaxation compared to nerol or isoproterenol alone. In looking at potential crosstalk between the signaling pathways, nerol-induced relaxation was not ablated by several TAS2R pathway inhibitors, nor β2AR pathway inhibitors, suggesting that these receptors may be acting through independent pathways to promote an additive effect of cell relaxation.
Conclusions: In this study, we showed an additive effect of ligands for odor, bitter taste, and β2 adrenergic receptors in magnifying human ASM cell relaxation compared to what each ligand could achieve alone. Therefore, sensory GPCRs show promise in being targets for both individual and combination therapies for asthma treatment.
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