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

Brichetto, Lorenzo, Manlio Milanese, Pingfang Song, Mauro Patrone, Emanuele Crimi, Kai Rehder, and Vito Brusasco. Beclomethasone rapidly ablates allergen-induced 2-adrenoceptor pathway dysfunction in human isolated bronchi. Am J Physiol Lung Cell Mol Physiol 284: L133–L139, 2003. First published August 16, 2002; 10.1152/ ajplung.00217.2002.—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 Gs 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. Gs protein expression was not significantly altered by BDP, suggesting that the activity of Gs 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 Gs protein in human isolated bronchi.