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The first potent \u03b22AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the \u03b22AR, epinephrine. In this study, we demonstrate that activation of the \u03b22AR 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 \u03b22AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase\u2013null mice restored the asthma phenotype. We conclude that \u03b22AR agonist\u2013induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the \u03b22AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of \u03b22AR 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 \u201c\u03b2-blockers.\u201d<\/jats:p>","DOI":"10.1165\/rcmb.2012-0364oc","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T02:32:32Z","timestamp":1354242752000},"page":"220-229","source":"Crossref","is-referenced-by-count":59,"title":["\u03b22-Adrenoceptor Agonists Are Required for Development of the Asthma Phenotype in a Murine Model"],"prefix":"10.1093","volume":"48","author":[{"given":"Vaidehi J.","family":"Thanawala","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria S.","family":"Forkuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Al-Sawalha","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoulikha","family":"Azzegagh","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, M.D. Anderson Cancer Center, University of Texas, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long P.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, M.D. Anderson Cancer Center, University of Texas, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Tuvim","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, M.D. Anderson Cancer Center, University of Texas, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Lowder","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, University of Houston, Houston, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton F.","family":"Dickey","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, M.D. Anderson Cancer Center, University of Texas, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Knoll","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia K. 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