Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.
Identifieur interne : 001623 ( Main/Exploration ); précédent : 001622; suivant : 001624Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.
Auteurs : Deepak A. Deshpande [États-Unis] ; Wayne C H. Wang ; Elizabeth L. Mcilmoyle ; Kathryn S. Robinett ; Rachel M. Schillinger ; Steven S. An ; James S K. Sham ; Stephen B. LiggettSource :
- Nature medicine [ 1546-170X ] ; 2010.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN messager (métabolisme), Animaux, Asthme (), Asthme (métabolisme), Asthme (physiopathologie), Bronches (), Bronches (anatomopathologie), Bronches (métabolisme), Bronches (physiopathologie), Bronchoconstriction (), Bronchoconstriction (physiologie), Canaux potassiques calcium-dépendants de grande conductance (métabolisme), Goût (), Goût (physiologie), Humains, Muscles lisses (), Muscles lisses (anatomopathologie), Muscles lisses (métabolisme), Muscles lisses (physiopathologie), Myocytes du muscle lisse (anatomopathologie), Myocytes du muscle lisse (métabolisme), Obstruction des voies aériennes (anatomopathologie), Obstruction des voies aériennes (métabolisme), Obstruction des voies aériennes (physiopathologie), Potentiels de membrane (), Potentiels de membrane (physiologie), Relation dose-effet des médicaments, Relâchement musculaire (), Relâchement musculaire (physiologie), Récepteurs couplés aux protéines G (génétique), Récepteurs couplés aux protéines G (métabolisme), Régulation de l'expression des gènes (), Saccharine (pharmacologie), Signalisation du calcium (), Souris, Séparation cellulaire.
- MESH :
- anatomopathologie : Bronches, Muscles lisses, Myocytes du muscle lisse, Obstruction des voies aériennes.
- génétique : ARN messager, Récepteurs couplés aux protéines G.
- métabolisme : ARN messager, Asthme, Bronches, Canaux potassiques calcium-dépendants de grande conductance, Muscles lisses, Myocytes du muscle lisse, Obstruction des voies aériennes, Récepteurs couplés aux protéines G.
- pharmacologie : Saccharine.
- physiologie : Bronchoconstriction, Goût, Potentiels de membrane, Relâchement musculaire.
- physiopathologie : Asthme, Bronches, Muscles lisses, Obstruction des voies aériennes.
- Animaux, Asthme, Bronches, Bronchoconstriction, Goût, Humains, Muscles lisses, Potentiels de membrane, Relation dose-effet des médicaments, Relâchement musculaire, Régulation de l'expression des gènes, Signalisation du calcium, Souris, Séparation cellulaire.
English descriptors
- KwdEn :
- Airway Obstruction (metabolism), Airway Obstruction (pathology), Airway Obstruction (physiopathology), Animals, Asthma (complications), Asthma (metabolism), Asthma (physiopathology), Bronchi (drug effects), Bronchi (metabolism), Bronchi (pathology), Bronchi (physiopathology), Bronchoconstriction (drug effects), Bronchoconstriction (physiology), Calcium Signaling (drug effects), Cell Separation, Dose-Response Relationship, Drug, Gene Expression Regulation (drug effects), Humans, Large-Conductance Calcium-Activated Potassium Channels (metabolism), Membrane Potentials (drug effects), Membrane Potentials (physiology), Mice, Muscle Relaxation (drug effects), Muscle Relaxation (physiology), Muscle, Smooth (drug effects), Muscle, Smooth (metabolism), Muscle, Smooth (pathology), Muscle, Smooth (physiopathology), Myocytes, Smooth Muscle (metabolism), Myocytes, Smooth Muscle (pathology), RNA, Messenger (genetics), RNA, Messenger (metabolism), Receptors, G-Protein-Coupled (genetics), Receptors, G-Protein-Coupled (metabolism), Saccharin (pharmacology), Taste (drug effects), Taste (physiology).
- MESH :
- chemical , genetics : RNA, Messenger, Receptors, G-Protein-Coupled.
- chemical , metabolism : Large-Conductance Calcium-Activated Potassium Channels, RNA, Messenger, Receptors, G-Protein-Coupled.
- complications : Asthma.
- drug effects : Bronchi, Bronchoconstriction, Calcium Signaling, Gene Expression Regulation, Membrane Potentials, Muscle Relaxation, Muscle, Smooth, Taste.
- metabolism : Airway Obstruction, Asthma, Bronchi, Muscle, Smooth, Myocytes, Smooth Muscle.
- pathology : Airway Obstruction, Bronchi, Muscle, Smooth, Myocytes, Smooth Muscle.
- chemical , pharmacology : Saccharin.
- physiology : Bronchoconstriction, Membrane Potentials, Muscle Relaxation, Taste.
- physiopathology : Airway Obstruction, Asthma, Bronchi, Muscle, Smooth.
- Animals, Cell Separation, Dose-Response Relationship, Drug, Humans, Mice.
Abstract
Bitter taste receptors (TAS2Rs) on the tongue probably evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants that, when activated, lead to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased intracellular calcium ([Ca²(+)](i)) in ASM in a Gβγ-, phospholipase Cβ (PLCβ)- and inositol trisphosphate (IP₃) receptor-dependent manner, which would be expected to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM and dilation of airways that was threefold greater than that elicited by β-adrenergic receptor agonists. The relaxation induced by TAS2Rs is associated with a localized [Ca²(+)](i) response at the cell membrane, which opens large-conductance Ca²(+)-activated K(+) (BK(Ca)) channels, leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in a mouse model of asthma. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants.
DOI: 10.1038/nm.2237
PubMed: 20972434
Affiliations:
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Wang</name></author><author><name sortKey="Mcilmoyle, Elizabeth L" sort="Mcilmoyle, Elizabeth L" uniqKey="Mcilmoyle E" first="Elizabeth L" last="Mcilmoyle">Elizabeth L. Mcilmoyle</name></author><author><name sortKey="Robinett, Kathryn S" sort="Robinett, Kathryn S" uniqKey="Robinett K" first="Kathryn S" last="Robinett">Kathryn S. Robinett</name></author><author><name sortKey="Schillinger, Rachel M" sort="Schillinger, Rachel M" uniqKey="Schillinger R" first="Rachel M" last="Schillinger">Rachel M. Schillinger</name></author><author><name sortKey="An, Steven S" sort="An, Steven S" uniqKey="An S" first="Steven S" last="An">Steven S. An</name></author><author><name sortKey="Sham, James S K" sort="Sham, James S K" uniqKey="Sham J" first="James S K" last="Sham">James S K. Sham</name></author><author><name sortKey="Liggett, Stephen B" sort="Liggett, Stephen B" uniqKey="Liggett S" first="Stephen B" last="Liggett">Stephen B. 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Calcium-Activated Potassium Channels (metabolism)</term><term>Membrane Potentials (drug effects)</term><term>Membrane Potentials (physiology)</term><term>Mice</term><term>Muscle Relaxation (drug effects)</term><term>Muscle Relaxation (physiology)</term><term>Muscle, Smooth (drug effects)</term><term>Muscle, Smooth (metabolism)</term><term>Muscle, Smooth (pathology)</term><term>Muscle, Smooth (physiopathology)</term><term>Myocytes, Smooth Muscle (metabolism)</term><term>Myocytes, Smooth Muscle (pathology)</term><term>RNA, Messenger (genetics)</term><term>RNA, Messenger (metabolism)</term><term>Receptors, G-Protein-Coupled (genetics)</term><term>Receptors, G-Protein-Coupled (metabolism)</term><term>Saccharin (pharmacology)</term><term>Taste (drug effects)</term><term>Taste (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>Animaux</term><term>Asthme ()</term><term>Asthme 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type="abstract" xml:lang="en">Bitter taste receptors (TAS2Rs) on the tongue probably evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants that, when activated, lead to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased intracellular calcium ([Ca²(+)](i)) in ASM in a Gβγ-, phospholipase Cβ (PLCβ)- and inositol trisphosphate (IP₃) receptor-dependent manner, which would be expected to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM and dilation of airways that was threefold greater than that elicited by β-adrenergic receptor agonists. The relaxation induced by TAS2Rs is associated with a localized [Ca²(+)](i) response at the cell membrane, which opens large-conductance Ca²(+)-activated K(+) (BK(Ca)) channels, leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in a mouse model of asthma. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="An, Steven S" sort="An, Steven S" uniqKey="An S" first="Steven S" last="An">Steven S. An</name><name sortKey="Liggett, Stephen B" sort="Liggett, Stephen B" uniqKey="Liggett S" first="Stephen B" last="Liggett">Stephen B. Liggett</name><name sortKey="Mcilmoyle, Elizabeth L" sort="Mcilmoyle, Elizabeth L" uniqKey="Mcilmoyle E" first="Elizabeth L" last="Mcilmoyle">Elizabeth L. Mcilmoyle</name><name sortKey="Robinett, Kathryn S" sort="Robinett, Kathryn S" uniqKey="Robinett K" first="Kathryn S" last="Robinett">Kathryn S. Robinett</name><name sortKey="Schillinger, Rachel M" sort="Schillinger, Rachel M" uniqKey="Schillinger R" first="Rachel M" last="Schillinger">Rachel M. Schillinger</name><name sortKey="Sham, James S K" sort="Sham, James S K" uniqKey="Sham J" first="James S K" last="Sham">James S K. Sham</name><name sortKey="Wang, Wayne C H" sort="Wang, Wayne C H" uniqKey="Wang W" first="Wayne C H" last="Wang">Wayne C H. Wang</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Deshpande, Deepak A" sort="Deshpande, Deepak A" uniqKey="Deshpande D" first="Deepak A" last="Deshpande">Deepak A. Deshpande</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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