Beclomethasone rapidly ablates allergen-induced beta 2- adrenoceptor pathway dysfunction in human isolated bronchi

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 284; no. 1; pp. 133 - L139
• Main Authors: Brichetto, Lorenzo, Milanese, Manlio, Song, Pingfang, Patrone, Mauro, Crimi, Emanuele, Rehder, Kai, Brusasco, Vito
• Format: Journal Article
• Language: English
• Published: United States 01.01.2003
• Subjects: Adenylyl Cyclases - metabolism; Administration, Topical; Adrenergic beta-Agonists - pharmacology; Aged; Albuterol - pharmacology; Allergens - immunology; Anti-Inflammatory Agents - pharmacology; Beclomethasone - pharmacology; Bronchi - metabolism; Female; Glucocorticoids; GTP-Binding Protein alpha Subunits, Gi-Go - physiology; GTP-Binding Protein alpha Subunits, Gs - physiology; Humans; In Vitro Techniques; Middle Aged; Protein Isoforms - physiology; Receptors, Adrenergic, beta - physiology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00217.2002

Dipartimenti di Scienze Motorie e Riabilitative, di Medicina Interna, e di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy 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 2 -adrenoceptor ( 2 -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 2 -AR pathway dysfunction. Incubation with the G s 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. G s protein expression was not significantly altered by BDP, suggesting that the activity of G s protein was increased. Relaxation of challenged rings by forskolin was not significantly affected by BDP, suggesting that 2 -AR pathway dysfunction was proximal to the adenylyl cyclase. In conclusion, short-term (3-h) treatment with BDP after allergen challenge ablated 2 -AR pathway dysfunction by increasing the activity of the G s protein in human isolated bronchi. asthma; cholera toxin; corticosteroids; G s protein; passive sensitization