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Article: Glucocorticoids reduce tachykinin NK2 receptor expression in bovine tracheal smooth muscle

TitleGlucocorticoids reduce tachykinin NK2 receptor expression in bovine tracheal smooth muscle
Authors
Issue Date1998
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 1998, v. 344 n. 1, p. 99-106 How to Cite?
AbstractNeurokinin A is not only a potent bronchoconstrictor, but also has immuno-modulatory effects in animals and man, mediated via tachykinin NK2 receptors. We have examined the effect of the glucocorticoid, dexamethasone, on tachykinin NK2 receptor mRNA and the number of tachykinin NK2 receptors in bovine tracheal smooth muscle in vitro by Northern blot analysis using a human tachykinin NK2 receptor cDNA probe and receptor binding assay using [3H]SR48968 {(S)-N-methyl-N[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl) butyl]benzamide}. Tachykinin NK2 receptor mRNA showed a time-dependent suppression (62% reduction after 6 h at 10-7 M of dexamethasone), as well as a concentration-dependent suppression after the incubation with dexamethasone (IC50 = 1.3 x 10-8 M). This suppression was abolished by the glucocorticoid receptor antagonist, mifepristone (RU38486), indicating that dexamethasone acts via the glucocorticoid receptor. It was also abolished by the protein synthesis inhibitor, cycloheximide (10 μg/ml), indicating that new protein synthesis is required on this suppression. Using the RNA polymerase inhibitor actinomycin D (5 μg/ml), we showed that the stability of tachykinin NK2 receptor mRNA was not affected by dexamethasone (t( 1/4 ) = 5 h). Nuclear run-on assays revealed a 51% reduction in the rate of tachykinin NK2 receptor gene transcription after treatment with dexamethasone for 6 h. Radioligand binding assay using an selective tachykinin NK2 receptor antagonist, [3H]SR48968 showed a significant decrease in the number of receptor binding sites after 16 h (B(max) = 262 ± 23 versus 213 ± 13 fmol/mg protein for vehicle and dexamethasone treatment respectively, P < 0.05), with no significant change at the earlier time points. These results suggest that glucocorticoids act on glucocorticoid receptors to decrease tachykinin NK2 receptor expression by decreasing the rate of tachykinin NK2 receptor gene transcription.
Persistent Identifierhttp://hdl.handle.net/10722/162267
ISSN
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKatsunuma, Ten_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorBarnes, PJen_US
dc.date.accessioned2012-09-05T05:18:31Z-
dc.date.available2012-09-05T05:18:31Z-
dc.date.issued1998en_US
dc.identifier.citationEuropean Journal Of Pharmacology, 1998, v. 344 n. 1, p. 99-106en_US
dc.identifier.issn0014-2999en_US
dc.identifier.urihttp://hdl.handle.net/10722/162267-
dc.description.abstractNeurokinin A is not only a potent bronchoconstrictor, but also has immuno-modulatory effects in animals and man, mediated via tachykinin NK2 receptors. We have examined the effect of the glucocorticoid, dexamethasone, on tachykinin NK2 receptor mRNA and the number of tachykinin NK2 receptors in bovine tracheal smooth muscle in vitro by Northern blot analysis using a human tachykinin NK2 receptor cDNA probe and receptor binding assay using [3H]SR48968 {(S)-N-methyl-N[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl) butyl]benzamide}. Tachykinin NK2 receptor mRNA showed a time-dependent suppression (62% reduction after 6 h at 10-7 M of dexamethasone), as well as a concentration-dependent suppression after the incubation with dexamethasone (IC50 = 1.3 x 10-8 M). This suppression was abolished by the glucocorticoid receptor antagonist, mifepristone (RU38486), indicating that dexamethasone acts via the glucocorticoid receptor. It was also abolished by the protein synthesis inhibitor, cycloheximide (10 μg/ml), indicating that new protein synthesis is required on this suppression. Using the RNA polymerase inhibitor actinomycin D (5 μg/ml), we showed that the stability of tachykinin NK2 receptor mRNA was not affected by dexamethasone (t( 1/4 ) = 5 h). Nuclear run-on assays revealed a 51% reduction in the rate of tachykinin NK2 receptor gene transcription after treatment with dexamethasone for 6 h. Radioligand binding assay using an selective tachykinin NK2 receptor antagonist, [3H]SR48968 showed a significant decrease in the number of receptor binding sites after 16 h (B(max) = 262 ± 23 versus 213 ± 13 fmol/mg protein for vehicle and dexamethasone treatment respectively, P < 0.05), with no significant change at the earlier time points. These results suggest that glucocorticoids act on glucocorticoid receptors to decrease tachykinin NK2 receptor expression by decreasing the rate of tachykinin NK2 receptor gene transcription.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_US
dc.relation.ispartofEuropean Journal of Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCattleen_US
dc.subject.meshCycloheximide - Pharmacologyen_US
dc.subject.meshDexamethasone - Antagonists & Inhibitors - Pharmacologyen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshMuscle, Smooth - Drug Effects - Metabolismen_US
dc.subject.meshProtein Synthesis Inhibitors - Pharmacologyen_US
dc.subject.meshRna, Messenger - Genetics - Metabolismen_US
dc.subject.meshReceptors, Neurokinin-2 - Drug Effects - Geneticsen_US
dc.subject.meshTrachea - Drug Effects - Metabolismen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.titleGlucocorticoids reduce tachykinin NK2 receptor expression in bovine tracheal 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.doi10.1016/S0014-2999(97)01562-8en_US
dc.identifier.pmid9570454-
dc.identifier.scopuseid_2-s2.0-0032567915en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032567915&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume344en_US
dc.identifier.issue1en_US
dc.identifier.spage99en_US
dc.identifier.epage106en_US
dc.identifier.isiWOS:000072852300015-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridKatsunuma, T=7004760540en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US

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