The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea
Identifieur interne : 001450 ( Main/Exploration ); précédent : 001449; suivant : 001451The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea
Auteurs : Ville Pulkkinen [Suède, Finlande] ; Martijn L. Manson [Suède] ; Jesper Safholm [Suède] ; Mikael Adner [Suède] ; Sven-Erik Dahlen [Suède]Source :
- American journal of physiology. Lung cellular and molecular physiology [ 1040-0605 ] ; 2012.
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- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Activation of taste receptors (TAS2Rs) by bitter taste agonists has been reported to cause bronchodilation. The aim of this study was to extend the information on the effects of bitter taste agonists on responses induced by different contractile mediators in a standard airway physiology preparation. Isometric responses were assessed in guinea pig trachea (GPT). TAS2R agonists were administered either to segments precontracted with different agonists for contraction or given before challenge with the different contractile stimuli, including antigen in tissues from ovalbumin-sensitized animals. TAS2R mRNA expression on GPT epithelium and smooth muscle was measured with real-time PCR. Denatonium, chloroquine, thiamine, and noscapine induced concentration-dependent relaxations (Rmax: 98.3 ± 1.6, 100.0 ± 0.0, 100.0 ± 0.0, and 52.3 ± 1.1% of maximum, respectively, in the presence of indomethacin) in segments precontracted with carbachol. The receptors for denatonium (TAS2R4, TAS2R10) and chloroquine (TAS2R3, TAS2R10) were expressed in GPT. Whereas denatonium selectively inhibited contractions induced by carbachol, chloroquine uniformly inhibited contractions evoked by prostaglandin E2, the thromboxane receptor agonist U-46619, leukotriene D4, histamine, and antigen. The effects of denatonium, but not those of chloroquine, were partly inhibited by blockers of the large Ca2+-activated K+ channels and decreased by an increase of the level of precontraction. In conclusion, TAS2R agonists mediated strong relaxations and substantial inhibition of contractions in GPT. Chloroquine and denatonium had distinct patterns of activity, indicating different signaling mechanisms. The findings reinforce the hypothesis that TAS2Rs are potential targets for the development of a new class of more efficacious agonists for bronchodilation.
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Manson</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>The Unit for Asthma and Allergy Research, the National Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Safholm, Jesper" sort="Safholm, Jesper" uniqKey="Safholm J" first="Jesper" last="Safholm">Jesper Safholm</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>The Unit for Asthma and Allergy Research, the National Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Adner, Mikael" sort="Adner, Mikael" uniqKey="Adner M" first="Mikael" last="Adner">Mikael Adner</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>The Unit for Asthma and Allergy Research, the National Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Dahlen, Sven Erik" sort="Dahlen, Sven Erik" uniqKey="Dahlen S" first="Sven-Erik" last="Dahlen">Sven-Erik Dahlen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>The Unit for Asthma and Allergy Research, the National Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author></analytic><series><title level="j" type="main">American journal of physiology. Lung cellular and molecular physiology</title><title level="j" type="abbreviated">Am. j. physiol., Lung cell. mol. physiol.</title><idno type="ISSN">1040-0605</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of physiology. Lung cellular and molecular physiology</title><title level="j" type="abbreviated">Am. j. physiol., Lung cell. mol. physiol.</title><idno type="ISSN">1040-0605</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Agonist</term><term>Asthma</term><term>Biological receptor</term><term>Bronchodilation</term><term>Chloroquine</term><term>Guinea pig</term><term>Mammalia</term><term>Prostaglandin</term><term>Relaxation</term><term>Respiratory system</term><term>Respiratory tract</term><term>Smooth muscle</term><term>Taste</term><term>Trachea</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Saveur</term><term>Récepteur biologique</term><term>Agoniste</term><term>Chloroquine</term><term>Relaxation</term><term>Trachée</term><term>Bronchodilatation</term><term>Asthme</term><term>Prostaglandine</term><term>Voie respiratoire</term><term>Muscle lisse</term><term>Mammalia</term><term>Cobaye</term><term>Appareil respiratoire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Activation of taste receptors (TAS2Rs) by bitter taste agonists has been reported to cause bronchodilation. The aim of this study was to extend the information on the effects of bitter taste agonists on responses induced by different contractile mediators in a standard airway physiology preparation. Isometric responses were assessed in guinea pig trachea (GPT). TAS2R agonists were administered either to segments precontracted with different agonists for contraction or given before challenge with the different contractile stimuli, including antigen in tissues from ovalbumin-sensitized animals. TAS2R mRNA expression on GPT epithelium and smooth muscle was measured with real-time PCR. Denatonium, chloroquine, thiamine, and noscapine induced concentration-dependent relaxations (R<sub>max</sub>: 98.3 ± 1.6, 100.0 ± 0.0, 100.0 ± 0.0, and 52.3 ± 1.1% of maximum, respectively, in the presence of indomethacin) in segments precontracted with carbachol. The receptors for denatonium (TAS2R4, TAS2R10) and chloroquine (TAS2R3, TAS2R10) were expressed in GPT. Whereas denatonium selectively inhibited contractions induced by carbachol, chloroquine uniformly inhibited contractions evoked by prostaglandin E<sub>2</sub>, the thromboxane receptor agonist U-46619, leukotriene D<sub>4</sub>, histamine, and antigen. The effects of denatonium, but not those of chloroquine, were partly inhibited by blockers of the large Ca<sup>2+</sup>-activated K<sup>+</sup> channels and decreased by an increase of the level of precontraction. In conclusion, TAS2R agonists mediated strong relaxations and substantial inhibition of contractions in GPT. Chloroquine and denatonium had distinct patterns of activity, indicating different signaling mechanisms. The findings reinforce the hypothesis that TAS2Rs are potential targets for the development of a new class of more efficacious agonists for bronchodilation.</div></front></TEI><affiliations><list><country><li>Finlande</li><li>Suède</li></country><region><li>Svealand</li><li>Uusimaa</li></region><settlement><li>Helsinki</li><li>Stockholm</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Pulkkinen, Ville" sort="Pulkkinen, Ville" uniqKey="Pulkkinen V" first="Ville" last="Pulkkinen">Ville Pulkkinen</name></region><name sortKey="Adner, Mikael" sort="Adner, Mikael" uniqKey="Adner M" first="Mikael" last="Adner">Mikael Adner</name><name sortKey="Dahlen, Sven Erik" sort="Dahlen, Sven Erik" uniqKey="Dahlen S" first="Sven-Erik" last="Dahlen">Sven-Erik Dahlen</name><name sortKey="Manson, Martijn L" sort="Manson, Martijn L" uniqKey="Manson M" first="Martijn L." last="Manson">Martijn L. Manson</name><name sortKey="Safholm, Jesper" sort="Safholm, Jesper" uniqKey="Safholm J" first="Jesper" last="Safholm">Jesper Safholm</name></country><country name="Finlande"><region name="Uusimaa"><name sortKey="Pulkkinen, Ville" sort="Pulkkinen, Ville" uniqKey="Pulkkinen V" first="Ville" last="Pulkkinen">Ville Pulkkinen</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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