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Article: Transgenic overexpression of β2-adrenergic receptors in airway epithelial cells decreases bronchoconstriction

TitleTransgenic overexpression of β2-adrenergic receptors in airway epithelial cells decreases bronchoconstriction
Authors
Issue Date2000
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajplung.physiology.org/
Citation
American Journal Of Physiology - Lung Cellular And Molecular Physiology, 2000, v. 279 n. 2 23-2, p. L379-L389 How to Cite?
AbstractAirway epithelial cells express β2-adrenergic receptors (β2-ARs), but their role in regulating airway responsiveness is unclear. With the Clara cell secretory protein (CCSP) promoter, we targeted expression of β2-ARs to airway epithelium of transgenic (CCSP-β2-AR) mice, thereby mimicking agonist activation of receptors only in these cells. In situ hybridization confirmed that transgene expression was confined to airway epithelium, and autoradiography showed that β2-AR density in CCSP-β2-AR mice was approximately twofold that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body plethysmography showed that the methacholine dose required to increase enhanced pause to 200% of baseline (ED200) was greater for CCSP-β2-AR than for NTG mice (345 ± 34 vs. 157 ± 14 mg/ml; P < 0.01). CCSP-β2-AR mice were also less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice acutely increased to 77% over baseline (P < 0.05) but remained unchanged in the CCSP-β2-AR mice. Although both groups were hyperreactive to methacholine 6 h after ozone exposure, the ED200 for ozone-exposed CCSP-β2-AR mice was equivalent to that for unexposed NTG mice. These findings show that epithelial cell β2-ARs regulate airway responsiveness in vivo and that the bronchodilating effect of β-agonists results from activation of receptors on both epithelial and smooth muscle cells.
Persistent Identifierhttp://hdl.handle.net/10722/162385
ISSN
2015 Impact Factor: 4.721
2015 SCImago Journal Rankings: 1.838
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMcgraw, DWen_US
dc.contributor.authorForbes, SLen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorWitte, DPen_US
dc.contributor.authorCarrigan, PEen_US
dc.contributor.authorLeikauf, GDen_US
dc.contributor.authorLiggett, SBen_US
dc.date.accessioned2012-09-05T05:19:28Z-
dc.date.available2012-09-05T05:19:28Z-
dc.date.issued2000en_US
dc.identifier.citationAmerican Journal Of Physiology - Lung Cellular And Molecular Physiology, 2000, v. 279 n. 2 23-2, p. L379-L389en_US
dc.identifier.issn1040-0605en_US
dc.identifier.urihttp://hdl.handle.net/10722/162385-
dc.description.abstractAirway epithelial cells express β2-adrenergic receptors (β2-ARs), but their role in regulating airway responsiveness is unclear. With the Clara cell secretory protein (CCSP) promoter, we targeted expression of β2-ARs to airway epithelium of transgenic (CCSP-β2-AR) mice, thereby mimicking agonist activation of receptors only in these cells. In situ hybridization confirmed that transgene expression was confined to airway epithelium, and autoradiography showed that β2-AR density in CCSP-β2-AR mice was approximately twofold that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body plethysmography showed that the methacholine dose required to increase enhanced pause to 200% of baseline (ED200) was greater for CCSP-β2-AR than for NTG mice (345 ± 34 vs. 157 ± 14 mg/ml; P < 0.01). CCSP-β2-AR mice were also less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice acutely increased to 77% over baseline (P < 0.05) but remained unchanged in the CCSP-β2-AR mice. Although both groups were hyperreactive to methacholine 6 h after ozone exposure, the ED200 for ozone-exposed CCSP-β2-AR mice was equivalent to that for unexposed NTG mice. These findings show that epithelial cell β2-ARs regulate airway responsiveness in vivo and that the bronchodilating effect of β-agonists results from activation of receptors on both epithelial and smooth muscle cells.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajplung.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Lung Cellular and Molecular Physiologyen_US
dc.subject.meshAdrenergic Beta-Agonists - Pharmacologyen_US
dc.subject.meshAdrenergic Beta-Antagonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Genetically Modified - Geneticsen_US
dc.subject.meshBronchoalveolar Lavage Fluid - Chemistryen_US
dc.subject.meshBronchoconstriction - Drug Effects - Geneticsen_US
dc.subject.meshDinoprostone - Analysisen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshHumansen_US
dc.subject.meshLung - Cytology - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMuscarinic Agonists - Pharmacologyen_US
dc.subject.meshNitric Oxide - Analysisen_US
dc.subject.meshOzone - Pharmacologyen_US
dc.subject.meshPlethysmography, Whole Bodyen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshProteins - Geneticsen_US
dc.subject.meshRna, Messenger - Biosynthesisen_US
dc.subject.meshReceptors, Adrenergic, Beta-2 - Biosynthesis - Geneticsen_US
dc.subject.meshRecombinant Fusion Proteins - Biosynthesis - Geneticsen_US
dc.subject.meshRespiratory Mucosa - Cytology - Metabolismen_US
dc.subject.meshSignal Transduction - Geneticsen_US
dc.subject.meshTransgenes - Geneticsen_US
dc.subject.meshUteroglobinen_US
dc.titleTransgenic overexpression of β2-adrenergic receptors in airway epithelial cells decreases bronchoconstrictionen_US
dc.typeArticleen_US
dc.identifier.emailMak, JCW:judymak@hku.hken_US
dc.identifier.authorityMak, JCW=rp00352en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10926562-
dc.identifier.scopuseid_2-s2.0-0033840465en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033840465&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume279en_US
dc.identifier.issue2 23-2en_US
dc.identifier.spageL379en_US
dc.identifier.epageL389en_US
dc.identifier.isiWOS:000088612800020-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMcGraw, DW=7005850346en_US
dc.identifier.scopusauthoridForbes, SL=7102524510en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridWitte, DP=35476712500en_US
dc.identifier.scopusauthoridCarrigan, PE=6602200320en_US
dc.identifier.scopusauthoridLeikauf, GD=7004899240en_US
dc.identifier.scopusauthoridLiggett, SB=7101758274en_US

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