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Article: Transforming growth factor-β1 induces transcriptional down-regulation of m2 muscarinic receptor gene expression

TitleTransforming growth factor-β1 induces transcriptional down-regulation of m2 muscarinic receptor gene expression
Authors
Issue Date1996
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.org
Citation
Molecular Pharmacology, 1996, v. 49 n. 5, p. 781-787 How to Cite?
AbstractIn human embryonic lung fibroblasts, transforming growth factor-β1 (TGF- β1) induced a time-dependent down-regulation of M2 muscarinic receptor binding sites as measured with the nonselective hydrophilic ligand [2H]N- methylscopolamine (NMS). This down-regulation was slow, with 58% loss of all receptors after 24 hr of treatment. The affinity of [3H]NMS for the remaining sites was unaltered by TGF-β1. The loss in [3H]NMS binding was accompanied by reduced adenylyl cyclase activity and functional desensitization of M2 muscarinic receptors. Northern blot analyses showed a 72% decrease in the steady state levels of m2 muscarinic receptor mRNA after 24-hr TGF-β1 treatment. Recovery of m2 muscarinic receptor mRNA after TGF- β1 treatment was slow, with a half-life of ~8 hr. There was no effect of TGF-β1 on the m2 muscarinic receptor mRNA half-life measured in the presence of actinomycin D, but the rate of m2 muscarinic receptor gene transcription measured with nuclear run-on assay was reduced by 50%, indicating reduced gene transcription. Cycloheximide (10 μg/ml) pretreatment abolished the TGF- β1 effect, indicating that de novo protein synthesis was required for receptor down-regulation. In summary, we have shown that TGF-β1 induced desensitization and down-regulation of M2 muscarinic receptor protein and gene that was mediated through reduction in the rate of m2 receptor gene transcription.
Persistent Identifierhttp://hdl.handle.net/10722/162147
ISSN
2015 Impact Factor: 3.931
2015 SCImago Journal Rankings: 2.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHaddad, EBen_US
dc.contributor.authorRousell, Jen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorBarnes, PJen_US
dc.date.accessioned2012-09-05T05:17:37Z-
dc.date.available2012-09-05T05:17:37Z-
dc.date.issued1996en_US
dc.identifier.citationMolecular Pharmacology, 1996, v. 49 n. 5, p. 781-787en_US
dc.identifier.issn0026-895Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/162147-
dc.description.abstractIn human embryonic lung fibroblasts, transforming growth factor-β1 (TGF- β1) induced a time-dependent down-regulation of M2 muscarinic receptor binding sites as measured with the nonselective hydrophilic ligand [2H]N- methylscopolamine (NMS). This down-regulation was slow, with 58% loss of all receptors after 24 hr of treatment. The affinity of [3H]NMS for the remaining sites was unaltered by TGF-β1. The loss in [3H]NMS binding was accompanied by reduced adenylyl cyclase activity and functional desensitization of M2 muscarinic receptors. Northern blot analyses showed a 72% decrease in the steady state levels of m2 muscarinic receptor mRNA after 24-hr TGF-β1 treatment. Recovery of m2 muscarinic receptor mRNA after TGF- β1 treatment was slow, with a half-life of ~8 hr. There was no effect of TGF-β1 on the m2 muscarinic receptor mRNA half-life measured in the presence of actinomycin D, but the rate of m2 muscarinic receptor gene transcription measured with nuclear run-on assay was reduced by 50%, indicating reduced gene transcription. Cycloheximide (10 μg/ml) pretreatment abolished the TGF- β1 effect, indicating that de novo protein synthesis was required for receptor down-regulation. In summary, we have shown that TGF-β1 induced desensitization and down-regulation of M2 muscarinic receptor protein and gene that was mediated through reduction in the rate of m2 receptor gene transcription.en_US
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.orgen_US
dc.relation.ispartofMolecular Pharmacologyen_US
dc.subject.meshAdenylate Cyclase - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCycloheximide - Pharmacologyen_US
dc.subject.meshDinoprostone - Pharmacologyen_US
dc.subject.meshDown-Regulation - Drug Effectsen_US
dc.subject.meshForskolin - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshProtein Synthesis Inhibitors - Pharmacologyen_US
dc.subject.meshRna, Messenger - Geneticsen_US
dc.subject.meshReceptors, Muscarinic - Geneticsen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshTransforming Growth Factor Beta - Pharmacologyen_US
dc.titleTransforming growth factor-β1 induces transcriptional down-regulation of m2 muscarinic receptor gene expressionen_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.pmid8622626-
dc.identifier.scopuseid_2-s2.0-0029928745en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029928745&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume49en_US
dc.identifier.issue5en_US
dc.identifier.spage781en_US
dc.identifier.epage787en_US
dc.identifier.isiWOS:A1996UK00400004-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHaddad, EB=7102803008en_US
dc.identifier.scopusauthoridRousell, J=6602560061en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US

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