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Article: β2-adrenoceptor agonist-induced upregulation of tachykinin NK2 receptor expression and function in airway smooth muscle

Titleβ2-adrenoceptor agonist-induced upregulation of tachykinin NK2 receptor expression and function in airway smooth muscle
Authors
Issue Date1999
PublisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.org
Citation
American Journal Of Respiratory Cell And Molecular Biology, 1999, v. 21 n. 3, p. 409-417 How to Cite?
AbstractNeurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because β2-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the β2-adrenoceptor agonist fenoterol on NK2 receptor messenger RNA (mRNA) and receptor density as well as the functional responses of bovine tracheal smooth muscle to the NK2 receptor agonist [β-Ala8]-NKA(4-10) in vitro, using Northern blot analysis, receptor binding, and organ bath studies. Incubation with fenoterol induced a time-and concentration-dependent upregulation of NK2 receptor mRNA (71% increase after 12 h at 10 7 M fenoterol), which was abolished by propranolol (a nonselective β-adrenoceptor agonist) and IC11 18551 (a selective β2-adrenoceptor antagonist), but not by CGP20712A (a selective β1-adrenoceptor antagonist), indicating that fenoterol acts via β2-adrenoceptors. These effects were mimicked by forskolin and prostaglandin E2 (PGE2), both agents that increase cyclic adenosine monophosphate (cAMP), and by the cAMP analogue 8-bromo-cAMP. The upregulation was blocked by cycloheximide, indicating that it requires new protein synthesis, and was accompanied by an increase in both the stability of NK2 receptor mRNA and the rate of NK2 receptor gene transcription. Radioligand binding assay using the selective NK2 receptor antagonist [3H]SR48968 showed a significant increase in the number of receptor binding sites after 12 h and 18 h, which was accompanied by an increased contractile responsiveness to the NK2 receptor agonist [β-Ala8]-NKA(4-10). Dexamethasone completely prevented the fenoterol-induced increase in NK2 receptor mRNA and in the contractile response. We conclude that β2-adrenoceptor agonists induce upregulation of functional NK2 receptors in airway smooth muscle by increasing cAMP, and that this can be prevented by a corticosteroid. The increased responsiveness could be relevant to asthma control and mortality.
Persistent Identifierhttp://hdl.handle.net/10722/162353
ISSN
2015 Impact Factor: 4.082
2015 SCImago Journal Rankings: 1.622
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKatsunuma, Ten_US
dc.contributor.authorRoffel, AFen_US
dc.contributor.authorElzinga, CRSen_US
dc.contributor.authorZaagsma, Jen_US
dc.contributor.authorBarnes, PJen_US
dc.contributor.authorMak, JCWen_US
dc.date.accessioned2012-09-05T05:19:13Z-
dc.date.available2012-09-05T05:19:13Z-
dc.date.issued1999en_US
dc.identifier.citationAmerican Journal Of Respiratory Cell And Molecular Biology, 1999, v. 21 n. 3, p. 409-417en_US
dc.identifier.issn1044-1549en_US
dc.identifier.urihttp://hdl.handle.net/10722/162353-
dc.description.abstractNeurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because β2-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the β2-adrenoceptor agonist fenoterol on NK2 receptor messenger RNA (mRNA) and receptor density as well as the functional responses of bovine tracheal smooth muscle to the NK2 receptor agonist [β-Ala8]-NKA(4-10) in vitro, using Northern blot analysis, receptor binding, and organ bath studies. Incubation with fenoterol induced a time-and concentration-dependent upregulation of NK2 receptor mRNA (71% increase after 12 h at 10 7 M fenoterol), which was abolished by propranolol (a nonselective β-adrenoceptor agonist) and IC11 18551 (a selective β2-adrenoceptor antagonist), but not by CGP20712A (a selective β1-adrenoceptor antagonist), indicating that fenoterol acts via β2-adrenoceptors. These effects were mimicked by forskolin and prostaglandin E2 (PGE2), both agents that increase cyclic adenosine monophosphate (cAMP), and by the cAMP analogue 8-bromo-cAMP. The upregulation was blocked by cycloheximide, indicating that it requires new protein synthesis, and was accompanied by an increase in both the stability of NK2 receptor mRNA and the rate of NK2 receptor gene transcription. Radioligand binding assay using the selective NK2 receptor antagonist [3H]SR48968 showed a significant increase in the number of receptor binding sites after 12 h and 18 h, which was accompanied by an increased contractile responsiveness to the NK2 receptor agonist [β-Ala8]-NKA(4-10). Dexamethasone completely prevented the fenoterol-induced increase in NK2 receptor mRNA and in the contractile response. We conclude that β2-adrenoceptor agonists induce upregulation of functional NK2 receptors in airway smooth muscle by increasing cAMP, and that this can be prevented by a corticosteroid. The increased responsiveness could be relevant to asthma control and mortality.en_US
dc.languageengen_US
dc.publisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.orgen_US
dc.relation.ispartofAmerican Journal of Respiratory Cell and Molecular Biologyen_US
dc.subject.meshAdrenergic Beta-2 Receptor Agonistsen_US
dc.subject.meshAdrenergic Beta-Agonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnti-Inflammatory Agents - Pharmacologyen_US
dc.subject.meshCattleen_US
dc.subject.meshDexamethasone - Pharmacologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshFenoterol - Pharmacologyen_US
dc.subject.meshMuscle, Smooth - Drug Effects - Metabolismen_US
dc.subject.meshNeurokinin A - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshOrgan Culture Techniquesen_US
dc.subject.meshPeptide Fragments - Pharmacologyen_US
dc.subject.meshRna, Messenger - Metabolismen_US
dc.subject.meshReceptors, Neurokinin-2 - Drug Effects - Metabolismen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTrachea - Drug Effects - Metabolismen_US
dc.subject.meshUp-Regulationen_US
dc.titleβ2-adrenoceptor agonist-induced upregulation of tachykinin NK2 receptor expression and function in airway smooth muscleen_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.doi10.1165/ajrcmb.21.3.3662-
dc.identifier.pmid10460759-
dc.identifier.scopuseid_2-s2.0-0033194394en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033194394&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume21en_US
dc.identifier.issue3en_US
dc.identifier.spage409en_US
dc.identifier.epage417en_US
dc.identifier.isiWOS:000082674800016-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKatsunuma, T=7004760540en_US
dc.identifier.scopusauthoridRoffel, AF=7003590196en_US
dc.identifier.scopusauthoridElzinga, CRS=6701648214en_US
dc.identifier.scopusauthoridZaagsma, J=16489795900en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US

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