{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T21:13:54Z","timestamp":1782767634749,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI110007"],"award-info":[{"award-number":["R01AI110007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Our previous studies have shown the \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor and its endogenous ligand, adrenaline, are required for development of the asthma phenotype in murine asthma models. Chronic administration of some, but not other, \u03b2\u2010blockers attenuated the asthma phenotype and led us to hypothesize that biased signalling was the basis of their differential effects, experimentally and clinically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used mice with no detectable systemic adrenaline (PNMT<jats:sup>\u2010\/\u2010<\/jats:sup>) and wild\u2010type (WT) mice to study the effects of four \u03b2\u2010blockers, alprenolol, carvedilol, propranolol and nadolol, in an ovalbumin sensitization and challenge (Ova S\/C) murine model of asthma. The parameters measured were inflammatory cell infiltration, mucous metaplasia and airway hyperresponsiveness. To interpret the pharmacological action of these ligands quantitatively, we conducted computer simulations of three\u2010state models of receptor activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Ova S\/C PNMT<jats:sup>\u2010\/\u2010<\/jats:sup> mice do not develop an asthma phenotype. Here, we showed that administration of alprenolol, carvedilol or propranolol in the absence of interference from adrenaline using Ova S\/C PNMT<jats:sup>\u2010\/\u2010<\/jats:sup> mice resulted in the development of an asthma phenotype, whereas nadolol had no effect. Ova S\/C WT mice did develop an asthma phenotype, and administration of alprenolol, propranolol and carvedilol had no effect on the asthma phenotype. However, nadolol prevented development of the asthma phenotype in Ova S\/C WT mice. Computer simulations of these four ligands were consistent with the isolated three\u2010state receptor model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>\u03b2\u2010Blockers have different effects on the murine asthma phenotype that correlate with reported differences in activation or inhibition of downstream \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor signalling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13253","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T22:08:59Z","timestamp":1437775739000},"page":"4833-4846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["\u03b2\u2010Blockers have differential effects on the murine asthma phenotype"],"prefix":"10.1111","volume":"172","author":[{"given":"V J","family":"Thanawala","sequence":"first","affiliation":[{"name":"Department of Integrative and Biology Pharmacology University of Texas Health Science Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Valdez","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G S","family":"Forkuo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin, Milwaukee Institute for Drug Discovery  Milwaukee WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Parra","sequence":"additional","affiliation":[{"name":"Vapogenix, Inc.  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B J","family":"Knoll","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bouvier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Universit\u00e9 de Montr\u00e9al  Montr\u00e9al QC Canada"},{"name":"Institute for Research in Immunology and Cancer Universit\u00e9 de Montr\u00e9al  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Leff","sequence":"additional","affiliation":[{"name":"Consultant in Pharmacology  Cheshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12445"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12451"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132559"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140249"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1936664100"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.3.679"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400452101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.7053"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20188"},{"key":"e_1_2_10_11_1","unstructured":"FoundationAA(2014). 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