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Article: Transcriptional down-regulation of m2 muscarinic receptor gene expression in human embryonic lung (HEL 299) cells by protein kinase C

TitleTranscriptional down-regulation of m2 muscarinic receptor gene expression in human embryonic lung (HEL 299) cells by protein kinase C
Authors
Issue Date1995
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1995, v. 270 n. 13, p. 7213-7218 How to Cite?
Abstractm2 muscarinic receptor gene expression was investigated following stimulation of protein kinase C (PKC) with the phorbol ester 4β-phorbol dibutyrate (PDBu) in HEL 299 cells. PDBu (100 nM) caused a time-dependent decrease in the steady-state levels of m2 receptor mRNA and in specific [3H]N-methyl-scopolamine binding. Preincubation with the PKC inhibitor GF- 109203X inhibited the reduction in M2 receptor and mRNA levels induced by PDBu, confirming the involvement of PKC. Chronic PDBu treatment also caused desensitization of the receptor as forskolin-stimulated cAMP accumulation, inhibited by carbachol in control cells, was lost upon treatment with PDBu for 24 h. Co-incubation with PDBu and the protein synthesis inhibitor cycloheximide, inhibited PDBu-mediated reduction of m2 receptor mRNA, indicating new protein synthesis is required for down-regulation. Half-life studies using the transcriptional inhibitor actinomycin D suggested that the stability of the m2 receptor mRNA was not altered by PDBu treatment (t( 1/2 ) = 2 h). Nuclear run-on assays showed a 50% reduction in the rate of m2 receptor gene transcription after treatment with PDBu for 12 h. In conclusion we have provided evidence for heterologous regulation of m2 receptor gene expression through changes in gene transcription resulting in uncoupling of M2 receptors. Furthermore, the synthesis of an unidentified factor is required for the down-regulation process.
Persistent Identifierhttp://hdl.handle.net/10722/162076
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151

 

DC FieldValueLanguage
dc.contributor.authorRousell, Jen_US
dc.contributor.authorHaddad, EBen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorBarnes, PJen_US
dc.date.accessioned2012-09-05T05:17:05Z-
dc.date.available2012-09-05T05:17:05Z-
dc.date.issued1995en_US
dc.identifier.citationJournal Of Biological Chemistry, 1995, v. 270 n. 13, p. 7213-7218en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/162076-
dc.description.abstractm2 muscarinic receptor gene expression was investigated following stimulation of protein kinase C (PKC) with the phorbol ester 4β-phorbol dibutyrate (PDBu) in HEL 299 cells. PDBu (100 nM) caused a time-dependent decrease in the steady-state levels of m2 receptor mRNA and in specific [3H]N-methyl-scopolamine binding. Preincubation with the PKC inhibitor GF- 109203X inhibited the reduction in M2 receptor and mRNA levels induced by PDBu, confirming the involvement of PKC. Chronic PDBu treatment also caused desensitization of the receptor as forskolin-stimulated cAMP accumulation, inhibited by carbachol in control cells, was lost upon treatment with PDBu for 24 h. Co-incubation with PDBu and the protein synthesis inhibitor cycloheximide, inhibited PDBu-mediated reduction of m2 receptor mRNA, indicating new protein synthesis is required for down-regulation. Half-life studies using the transcriptional inhibitor actinomycin D suggested that the stability of the m2 receptor mRNA was not altered by PDBu treatment (t( 1/2 ) = 2 h). Nuclear run-on assays showed a 50% reduction in the rate of m2 receptor gene transcription after treatment with PDBu for 12 h. In conclusion we have provided evidence for heterologous regulation of m2 receptor gene expression through changes in gene transcription resulting in uncoupling of M2 receptors. Furthermore, the synthesis of an unidentified factor is required for the down-regulation process.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshBlotting, Northernen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Nucleus - Metabolismen_US
dc.subject.meshCycloheximide - Pharmacologyen_US
dc.subject.meshDactinomycin - Pharmacologyen_US
dc.subject.meshEmbryo, Mammalianen_US
dc.subject.meshForskolin - Pharmacologyen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHalf-Lifeen_US
dc.subject.meshHumansen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshLungen_US
dc.subject.meshMaleimides - Pharmacologyen_US
dc.subject.meshN-Methylscopolamineen_US
dc.subject.meshPhorbol 12,13-Dibutyrate - Pharmacologyen_US
dc.subject.meshProtein Kinase C - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshRna, Messenger - Analysis - Biosynthesisen_US
dc.subject.meshReceptors, Muscarinic - Biosynthesis - Metabolismen_US
dc.subject.meshScopolamine Derivatives - Metabolismen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.titleTranscriptional down-regulation of m2 muscarinic receptor gene expression in human embryonic lung (HEL 299) cells by protein kinase Cen_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.doi10.1074/jbc.270.13.7213en_US
dc.identifier.pmid7706260-
dc.identifier.scopuseid_2-s2.0-0028920563en_US
dc.identifier.volume270en_US
dc.identifier.issue13en_US
dc.identifier.spage7213en_US
dc.identifier.epage7218en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridRousell, J=6602560061en_US
dc.identifier.scopusauthoridHaddad, EB=7102803008en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US

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