Details

Autor(en) / Beteiligte

• Thanawala, Vaidehi J
• Forkuo, Gloria S
• Al-Sawalha, Nour
• Azzegagh, Zoulikha
• Nguyen, Long P
• Eriksen, Jason L
• Tuvim, Michael J
• Lowder, Thomas W
• Dickey, Burton F
• Knoll, Brian J
• Walker, Julia K L
• Bond, Richard A

Titel

[Beta]2-Adrenoceptor Agonists Are Required for Development of the Asthma Phenotype in a Murine Model

Ist Teil von

• American journal of respiratory cell and molecular biology, 2013-02, Vol.48 (2), p.220

Ort / Verlag

New York: American Thoracic Society

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• [beta](2)-Adrenoceptor ([beta]2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent [beta]2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the [beta]2AR, epinephrine. In this study, we demonstrate that activation of the [beta]2AR by epinephrine is paradoxically required for development of the asthma phenotype. In an antigen-driven model, mice sensitized and challenged with ovalbumin showed marked elevations in three cardinal features of the asthma phenotype: inflammatory cells in their bronchoalveolar lavage fluid, mucin over production, and airway hyperresponsiveness. However, genetic depletion of epinephrine using mice lacking the enzyme to synthesize epinephrine, phenylethanolamine N-methyltransferase, or mice that had undergone pharmacological sympathectomy with reserpine to deplete epinephrine, had complete attenuation of these three cardinal features of the asthma phenotype. Furthermore, administration of the long-acting [beta]2AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase-null mice restored the asthma phenotype. We conclude that [beta]2AR agonist-induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the [beta]2AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of [beta]2AR agonists, such as formoterol, have been associated with adverse outcomes in asthma. These data further support the hypothesis that chronic asthma management may be better served by treatment with certain "[beta]-blockers."