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Am J Physiol Lung Cell Mol Physiol (August 16, 2002). doi:10.1152/ajplung.00217.2002
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Articles in PresS, published online ahead of print August 16, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00217.2002
Submitted on July 8, 2002
Accepted on August 14, 2002

Beclomethasone rapidly ablates allergen induced ß2-adrenoceptor pathway dysfunction in human isolated bronchi

Lorenzo Brichetto1, Manlio Milanese1, Pingfang Song2, Mauro Patrone3, Emanuele Crimi2, Kai Rehder1, and Vito Brusasco1*

1 Dipartimento di Medicina Interna, Universita di Genova, Genova, Italy
2 Dipartimento di Scienze Motorie e Riabilitative, Universita di Genova, Genova, Italy
3 Dipartimento di Medicina Sperimentale, Universita di Genova, Genova, Italy

* To whom correspondence should be addressed. E-mail: brusasco{at}dism.unige.it.

Bronchial rings from non-atopic humans were passively sensitized with serum from allergic subjects. Allergen challenge reduced significantly the relaxant effect of salbutamol on carbachol-induced contractions, suggesting ß2-adrenoceptor pathway dysfunction. Incubation of challenged rings for 3 h with beclomethasone dipropionate (BDP) 3x10-6M restored the relaxant effect, suggesting reversal of ß2-adrenoceptor pathway dysfunction. Incubation with the Gs{alpha}-protein stimulating cholera toxin (CTX) 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 CTX that was similar to that in unchallenged rings. Gs{alpha}-protein expression was not significantly altered by BDP, suggesting that the activity of Gs{alpha}-protein was increased. Relaxation of challenged rings by forskolin was not significantly affected by BDP, suggesting the ß2-adrenoceptor pathway dysfunction to be proximal to the adenylyl cyclase. In conclusion, short term (3 h) treatment with BDP after allergen challenge ablatedß2-adrenoceptor pathway dysfunction by increasing the activity of the Gs{alpha}-protein in human isolated bronchi.




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