当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY期刊下所有文献 > β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

Abstract：

:β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, we demonstrate that activation of the β2AR 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 β2AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase-null mice restored the asthma phenotype. We conclude that β2AR agonist-induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the β2AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of β2AR 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 "β-blockers."

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Thanawala VJ,Forkuo GS,Al-Sawalha N,Azzegagh Z,Nguyen LP,Eriksen JL,Tuvim MJ,Lowder TW,Dickey BF,Knoll BJ,Walker JK,Bond RA

doi

10.1165/rcmb.2012-0364OC

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

220-9

issue

eissn

1044-1549

issn

1535-4989

pii

rcmb.2012-0364OC

journal_volume

pub_type

杂志文章

在线工具

β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.