Beclomethasone rapidly ablates allergen-induced β2-adrenoceptor pathway dysfunction in human isolated bronchi
| Autor: | Kai Rehder, Lorenzo Brichetto, Vito Brusasco, Pingfang Song, Mauro Patrone, Emanuele Crimi, Manlio Milanese |
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| Předmět: |
Pulmonary and Respiratory Medicine
Physiology Administration Topical Anti-Inflammatory Agents Bronchi GTP-Binding Protein alpha Subunits Gi-Go In Vitro Techniques medicine.disease_cause Allergen Physiology (medical) Receptors Adrenergic beta GTP-Binding Protein alpha Subunits Gs medicine Humans Protein Isoforms Albuterol Respiratory system Glucocorticoids Sensitization Aged Asthma Bronchus business.industry Beclomethasone Cell Biology Beclometasone dipropionate Adrenergic beta-Agonists Allergens Middle Aged respiratory system medicine.disease medicine.anatomical_structure Immunology Salbutamol Female business Adenylyl Cyclases medicine.drug Respiratory tract |
| Zdroj: | Scopus-Elsevier |
| Popis: | Bronchial rings from nonatopic humans were passively sensitized with serum from allergic subjects. Allergen challenge significantly reduced the relaxant effect of salbutamol on carbachol-induced contractions, suggesting β2-adrenoceptor (β2-AR) pathway dysfunction. Incubation of challenged rings for 3 h with 3 × 10−6 M beclomethasone dipropionate (BDP) restored the relaxant effect, suggesting reversal of β2-AR pathway dysfunction. Incubation with the Gsα protein-stimulating cholera toxin attenuated contractile responses to carbachol significantly less in challenged than in unchallenged rings. Treatment of challenged rings with BDP resulted in an inhibitory effect of cholera toxin that was similar to the effect in unchallenged rings. Gsα protein expression was not significantly altered by BDP, suggesting that the activity of Gsα protein was increased. Relaxation of challenged rings by forskolin was not significantly affected by BDP, suggesting that β2-AR pathway dysfunction was proximal to the adenylyl cyclase. In conclusion, short-term (3-h) treatment with BDP after allergen challenge ablated β2-AR pathway dysfunction by increasing the activity of the Gsα protein in human isolated bronchi. |
| Databáze: | OpenAIRE |
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