Allergic airway inflammation and beta-adrenoceptor dysfunction.
A reduced response to beta-adrenoceptor agonists has been reported in airways of asthmatic subjects. Mechanisms for beta-adrenoceptor dysfunction are (1) inactivation or downregulation of beta-adrenoceptors by specific agonists (homologous desensitization) or by inflammatory mediations (heterologous desensitization), (2) inactivation or downregulation of second messengers of beta-adrenoceptor pathway. Studies from our laboratory have shown that allergen challenge of passively sensitized human bronchi causes a beta-adrenoceptor dysfunction as a result of reduced activity of the receptor-coupled Gs protein. The dysfunction was prevented by leukotriene-receptor antagonists or a cell membrane stabilizer, but not by an antihistimine or indomethacin, suggesting a central role of leukotrienes released from resident inflammatory cells in its genesis. Furthermore, the beta-adrenoceptor response and Gs protein function after allergen exposure were restored by short-term (3 h) incubation with beclomethasone dipropionate, suggesting an effect independent of gene transcription. Restoration of the intracellular beta-adrenoceptor effector pathway may contribute to the efficacy of corticosteroids in the acute treatment of asthma.
Brusasco
Vito
V
Dipartimento di Medicina Interna, Università di Genova, Genoa, Italy. vito.brusasco@unige.it
Crimi
Emanuele
E
Baroffio
Michele
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D001507:Beclomethasone / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000485:Allergens; D020024:Leukotriene Antagonists; D011943:Receptors, Adrenergic, beta; D001507:Beclomethasone