Beclomethasone rapidly ablates allergen-induced beta 2-adrenoceptor pathway dysfunction in human isolated bronchi.
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 beta(2)-adrenoceptor (beta(2)-AR) pathway dysfunction. Incubation of challenged rings for 3 h with 3 x 10(-6) M beclomethasone dipropionate (BDP) restored the relaxant effect, suggesting reversal of beta(2)-AR pathway dysfunction. Incubation with the G(s)alpha 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)alpha protein expression was not significantly altered by BDP, suggesting that the activity of G(s)alpha protein was increased. Relaxation of challenged rings by forskolin was not significantly affected by BDP, suggesting that beta(2)-AR pathway dysfunction was proximal to the adenylyl cyclase. In conclusion, short-term (3-h) treatment with BDP after allergen challenge ablated beta(2)-AR pathway dysfunction by increasing the activity of the G(s)alpha protein in human isolated bronchi.
Brichetto
Lorenzo
L
Dipartimenti di Scienze Motorie e Riabilitative, di Medicina Interna, e di Medicina Sperimentale, Università di Genova, Viale Benedetto XV 6, 16132 Genoa, Italy.
Milanese
Manlio
M
Song
Pingfang
P
Patrone
Mauro
M
Crimi
Emanuele
E
Rehder
Kai
K
Brusasco
Vito
V
D000262:Adenylyl Cyclases / Q000378:metabolism; D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001507:Beclomethasone / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology; D005938:Glucocorticoids; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D020033:Protein Isoforms / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000485:Allergens; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D020033:Protein Isoforms; D011943:Receptors, Adrenergic, beta; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D001507:Beclomethasone; D000420:Albuterol