The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea
Identifieur interne : 000061 ( PascalFrancis/Curation ); précédent : 000060; suivant : 000062The 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.
Descripteurs français
- 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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<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>
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, 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>
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<s5>57</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Respiratory system</s0>
<s5>57</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Aparato respiratorio</s0>
<s5>57</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Gustation</s0>
<s5>20</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Gustation</s0>
<s5>20</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Gusto</s0>
<s5>20</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Système gustatif</s0>
<s5>21</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Gustative system</s0>
<s5>21</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Sistema gustativo</s0>
<s5>21</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0>
<s5>22</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>22</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>22</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Bronchopneumopathie obstructive</s0>
<s5>23</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Obstructive pulmonary disease</s0>
<s5>23</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad pulmonar obstructiva</s0>
<s5>23</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Dérivé de l'acide arachidonique</s0>
<s5>24</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Arachidonic acid derivatives</s0>
<s5>24</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Araquidónico ácido derivado</s0>
<s5>24</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Eicosanoïde</s0>
<s5>25</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Eicosanoid</s0>
<s5>25</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Eicosanoide</s0>
<s5>25</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Pathologie des bronches</s0>
<s5>26</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Bronchus disease</s0>
<s5>26</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Bronquio patología</s0>
<s5>26</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Pathologie des poumons</s0>
<s5>27</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>27</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Pulmón patología</s0>
<s5>27</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fN21><s1>070</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>
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