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Article: Glucocorticoids reverse IL-1β-induced impairment of β-adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases

TitleGlucocorticoids reverse IL-1β-induced impairment of β-adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases
Authors
Issue Date2002
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2002, v. 135 n. 4, p. 987-996 How to Cite?
Abstract1. The aim of the present study was to examine the effects of glucocorticoid dexamethasone on airway responsiveness to albuterol after intratracheal instillation of saline or IL-1β in Brown-Norway rats in vivo and to elucidate the molecular mechanism of this effect. 2. IL-1β caused a significant reduction in albuterol-mediated relaxation to protect against MCh-induced bronchoconstriction. Dexamethasone attenuated the IL-1β-induced impaired relaxation while alone had no effect when compared to rats treated identically with saline. 3. The density of β 2-adrenoceptors was significantly reduced in lung membranes harvested from IL-1β-treated rats, which was associated with impaired isoproterenol- and forskolin-stimulated cyclic AMP accumulation and adenylyl cyclase (AC) activity ex vivo. Dexamethasone did not prevent IL-1β-induced down-regulation of β 2-adrenoceptors but completely blocked IL-1β-induced impairment of cyclic AMP accumulation and AC activity stimulated by isoproterenol and forskolin. 4. The inhibitory G-protein subtypes, G iα1, G iα2 and G iα3, were detected in lung membranes prepared from all groups of rats but the intensity of G iα1 and G iα2 was markedly increased in IL-1β-treated rats, which were not prevented by dexamethasone. 5. The activity of cytosolic GRK and the expression of GRK2 and GRK5 were elevated in the lung of IL-1β-treated rats, which were completely abolished by dexamethasone. 6. These results indicate that treatment of rats with IL-1β results in desensitization of pulmonary β 2-adrenoceptors. In light of data obtained in this study, we propose that both the decrease in AC activity and the increase in GRK activity, which are reversed by dexamethasone, may underlie β 2-adrenoceptor desensitization.
Persistent Identifierhttp://hdl.handle.net/10722/162589
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMak, JCWen_US
dc.contributor.authorHisada, Ten_US
dc.contributor.authorSalmon, Men_US
dc.contributor.authorBarnes, PJen_US
dc.contributor.authorChung, KFen_US
dc.date.accessioned2012-09-05T05:21:30Z-
dc.date.available2012-09-05T05:21:30Z-
dc.date.issued2002en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2002, v. 135 n. 4, p. 987-996en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/162589-
dc.description.abstract1. The aim of the present study was to examine the effects of glucocorticoid dexamethasone on airway responsiveness to albuterol after intratracheal instillation of saline or IL-1β in Brown-Norway rats in vivo and to elucidate the molecular mechanism of this effect. 2. IL-1β caused a significant reduction in albuterol-mediated relaxation to protect against MCh-induced bronchoconstriction. Dexamethasone attenuated the IL-1β-induced impaired relaxation while alone had no effect when compared to rats treated identically with saline. 3. The density of β 2-adrenoceptors was significantly reduced in lung membranes harvested from IL-1β-treated rats, which was associated with impaired isoproterenol- and forskolin-stimulated cyclic AMP accumulation and adenylyl cyclase (AC) activity ex vivo. Dexamethasone did not prevent IL-1β-induced down-regulation of β 2-adrenoceptors but completely blocked IL-1β-induced impairment of cyclic AMP accumulation and AC activity stimulated by isoproterenol and forskolin. 4. The inhibitory G-protein subtypes, G iα1, G iα2 and G iα3, were detected in lung membranes prepared from all groups of rats but the intensity of G iα1 and G iα2 was markedly increased in IL-1β-treated rats, which were not prevented by dexamethasone. 5. The activity of cytosolic GRK and the expression of GRK2 and GRK5 were elevated in the lung of IL-1β-treated rats, which were completely abolished by dexamethasone. 6. These results indicate that treatment of rats with IL-1β results in desensitization of pulmonary β 2-adrenoceptors. In light of data obtained in this study, we propose that both the decrease in AC activity and the increase in GRK activity, which are reversed by dexamethasone, may underlie β 2-adrenoceptor desensitization.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAdenylate Cyclase - Metabolismen_US
dc.subject.meshAdrenergic Beta-Agonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Northernen_US
dc.subject.meshCyclic Amp - Biosynthesisen_US
dc.subject.meshCyclic Amp-Dependent Protein Kinases - Metabolismen_US
dc.subject.meshDexamethasone - Pharmacologyen_US
dc.subject.meshG-Protein-Coupled Receptor Kinase 3en_US
dc.subject.meshG-Protein-Coupled Receptor Kinase 5en_US
dc.subject.meshGtp-Binding Protein Alpha Subunits, Gi-Go - Metabolismen_US
dc.subject.meshGtp-Binding Proteins - Metabolismen_US
dc.subject.meshGlucocorticoids - Pharmacologyen_US
dc.subject.meshInterleukin-1 - Pharmacologyen_US
dc.subject.meshLung - Drug Effects - Metabolism - Physiologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMuscle Relaxation - Drug Effectsen_US
dc.subject.meshProtein Isoforms - Metabolismen_US
dc.subject.meshProtein Kinases - Metabolismen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshRadioligand Assayen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptors, Adrenergic, Beta-2 - Metabolismen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshBeta-Adrenergic Receptor Kinasesen_US
dc.titleGlucocorticoids reverse IL-1β-induced impairment of β-adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinasesen_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.doi10.1038/sj.bjp.0704545-
dc.identifier.pmid11861327-
dc.identifier.scopuseid_2-s2.0-0036191962en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036191962&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume135en_US
dc.identifier.issue4en_US
dc.identifier.spage987en_US
dc.identifier.epage996en_US
dc.identifier.isiWOS:000174108300017-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridHisada, T=7004564760en_US
dc.identifier.scopusauthoridSalmon, M=7102527335en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US
dc.identifier.scopusauthoridChung, KF=35403525000en_US

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