ChloroquineV1, PascalFrancis, Checkpoint, bibRecord, 000009

TAS2R activation promotes airway smooth muscle relaxation despite β2-adrenergic receptor tachyphylaxis

Identifieur interne : 000009 ( PascalFrancis/Checkpoint ); précédent : 000008; suivant : 000010

TAS2R activation promotes airway smooth muscle relaxation despite β2-adrenergic receptor tachyphylaxis

Auteurs : Steven S. An [États-Unis] ; Wayne C. H. Wang [États-Unis] ; Cynthia J. Koziol-White [États-Unis] ; Kwangmi Ahn [États-Unis] ; Danielle Y. Lee [États-Unis] ; Richard C. Kurten [États-Unis] ; Reynold A. Jr Panettieri [États-Unis] ; Stephen B. Liggett [États-Unis]

Source :

American journal of physiology. Lung cellular and molecular physiology [ 1040-0605 ] ; 2012.

RBID : Pascal:12-0423718

Descripteurs français

Pascal (Inist)
- Activation, Voie respiratoire, Muscle lisse, Relaxation, Récepteur β2-adrénergique, Tachyphylaxie, Asthme, Désensibilisation, Chloroquine, Saveur, Récepteur biologique, Mammalia, Appareil respiratoire.

English descriptors

KwdEn :
- Activation, Asthma, Biological receptor, Chloroquine, Desensitization, Mammalia, Relaxation, Respiratory system, Respiratory tract, Smooth muscle, Tachyphylaxis, Taste, β2-Adrenergic receptor.

Abstract

Recently, bitter taste receptors (TAS2Rs) were found in the lung and act to relax airway smooth muscle (ASM) via intracellular Ca²⁺ concentration signaling generated from restricted phospholipase C activation. As potential therapy, TAS2R agonists could be add-on treatment when patients fail to achieve adequate bronchodilation with chronic β-agonists. The β₂-adrenergic receptor (β₂AR) of ASM undergoes extensive functional desensitization. It remains unknown whether this desensitization affects TAS2R function, by cross talk at the receptors or distal common components in the relaxation machinery. We studied intracellular signaling and cell mechanics using isolated human ASM, mouse tracheal responses, and human bronchial responses to characterize TAS2R relaxation in the context of β₂AR desensitization. In isolated human ASM, magnetic twisting cytometry revealed >90% loss of isoproterenol-promoted decrease in cell stiffness after 18-h exposure to albuterol. Under these same conditions of β₂AR desensitization, the TAS2R agonist chloroquine relaxation response was unaffected. TAS2R-mediated stimulation of intracellular Ca²⁺ concentration in human ASM was unaltered by albuterol pretreatment, in contrast to cAMP signaling, which was desensitized by >90%. In mouse trachea, β₂AR desensitization by β-agonist amounted to 92 ± 6.0% (P < 0.001), while, under these same conditions, TAS2R desensitization was not significant (11 ± 3.5%). In human lung slices, chronic β-agonist exposure culminated in 64 ± 5.7% (P < 0.001) desensitization of β₂AR-mediated dilation of carbachol-constricted airways that was reversed by chloroquine. We conclude that there is no evidence for physiologically relevant cross-desensitization of TAS2R-mediated ASM relaxation from chronic P-agonist treatment. These findings portend a favorable therapeutic profile for TAS2R agonists for the treatment of bronchospasm in asthma or chronic obstructive lung disease.

Affiliations:

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<front><div type="abstract" xml:lang="en">Recently, bitter taste receptors (TAS2Rs) were found in the lung and act to relax airway smooth muscle (ASM) via intracellular Ca<sup>2+</sup>
 concentration signaling generated from restricted phospholipase C activation. As potential therapy, TAS2R agonists could be add-on treatment when patients fail to achieve adequate bronchodilation with chronic β-agonists. The β<sub>2</sub>
-adrenergic receptor (β<sub>2</sub>
AR) of ASM undergoes extensive functional desensitization. It remains unknown whether this desensitization affects TAS2R function, by cross talk at the receptors or distal common components in the relaxation machinery. We studied intracellular signaling and cell mechanics using isolated human ASM, mouse tracheal responses, and human bronchial responses to characterize TAS2R relaxation in the context of β<sub>2</sub>
AR desensitization. In isolated human ASM, magnetic twisting cytometry revealed >90% loss of isoproterenol-promoted decrease in cell stiffness after 18-h exposure to albuterol. Under these same conditions of β<sub>2</sub>
AR desensitization, the TAS2R agonist chloroquine relaxation response was unaffected. TAS2R-mediated stimulation of intracellular Ca<sup>2+</sup>
 concentration in human ASM was unaltered by albuterol pretreatment, in contrast to cAMP signaling, which was desensitized by >90%. In mouse trachea, β<sub>2</sub>
AR desensitization by β-agonist amounted to 92 ± 6.0% (P < 0.001), while, under these same conditions, TAS2R desensitization was not significant (11 ± 3.5%). In human lung slices, chronic β-agonist exposure culminated in 64 ± 5.7% (P < 0.001) desensitization of β<sub>2</sub>
AR-mediated dilation of carbachol-constricted airways that was reversed by chloroquine. We conclude that there is no evidence for physiologically relevant cross-desensitization of TAS2R-mediated ASM relaxation from chronic P-agonist treatment. These findings portend a favorable therapeutic profile for TAS2R agonists for the treatment of bronchospasm in asthma or chronic obstructive lung disease.</div>
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<fC03 i1="04" i2="X" l="SPA"><s0>Relajación</s0>
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</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Récepteur β2-adrénergique</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>β2-Adrenergic receptor</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Receptor β2-adrenérgico</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Tachyphylaxie</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Tachyphylaxis</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Taquifilaxia</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Asthme</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Asthma</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Asma</s0>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Désensibilisation</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Desensitization</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Desensibilización</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Chloroquine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Chloroquine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Cloroquina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Saveur</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Taste</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Sabor</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Récepteur biologique</s0>
<s5>13</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Biological receptor</s0>
<s5>13</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Receptor biológico</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>14</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>14</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>14</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Appareil respiratoire</s0>
<s5>57</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Respiratory system</s0>
<s5>57</s5>
</fC03>
<fC03 i1="13" 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>Pathologie de l'appareil respiratoire</s0>
<s5>20</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>20</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>20</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Bronchopneumopathie obstructive</s0>
<s5>21</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Obstructive pulmonary disease</s0>
<s5>21</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad pulmonar obstructiva</s0>
<s5>21</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Gustation</s0>
<s5>22</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Gustation</s0>
<s5>22</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Gusto</s0>
<s5>22</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Système gustatif</s0>
<s5>23</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Gustative system</s0>
<s5>23</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Sistema gustativo</s0>
<s5>23</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Pathologie des bronches</s0>
<s5>24</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Bronchus disease</s0>
<s5>24</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Bronquio patología</s0>
<s5>24</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Pathologie des poumons</s0>
<s5>25</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>25</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Pulmón patología</s0>
<s5>25</s5>
</fC07>
<fN21><s1>331</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Arkansas</li>
<li>Floride</li>
<li>Maryland</li>
<li>Pennsylvanie</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Maryland"><name sortKey="An, Steven S" sort="An, Steven S" uniqKey="An S" first="Steven S." last="An">Steven S. An</name>
</region>
<name sortKey="Ahn, Kwangmi" sort="Ahn, Kwangmi" uniqKey="Ahn K" first="Kwangmi" last="Ahn">Kwangmi Ahn</name>
<name sortKey="Koziol White, Cynthia J" sort="Koziol White, Cynthia J" uniqKey="Koziol White C" first="Cynthia J." last="Koziol-White">Cynthia J. Koziol-White</name>
<name sortKey="Kurten, Richard C" sort="Kurten, Richard C" uniqKey="Kurten R" first="Richard C." last="Kurten">Richard C. Kurten</name>
<name sortKey="Lee, Danielle Y" sort="Lee, Danielle Y" uniqKey="Lee D" first="Danielle Y." last="Lee">Danielle Y. Lee</name>
<name sortKey="Liggett, Stephen B" sort="Liggett, Stephen B" uniqKey="Liggett S" first="Stephen B." last="Liggett">Stephen B. Liggett</name>
<name sortKey="Panettieri, Reynold A Jr" sort="Panettieri, Reynold A Jr" uniqKey="Panettieri R" first="Reynold A. Jr" last="Panettieri">Reynold A. Jr Panettieri</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>
</country>
</tree>
</affiliations>
</record>

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   |texte=   TAS2R activation promotes airway smooth muscle relaxation despite β2-adrenergic receptor tachyphylaxis
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Serveur d'exploration Chloroquine

TAS2R activation promotes airway smooth muscle relaxation despite β2-adrenergic receptor tachyphylaxis

TAS2R activation promotes airway smooth muscle relaxation despite β2-adrenergic receptor tachyphylaxis

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