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cAMP stimulates transcription of the beta 2-adrenergic receptor gene in response to short-term agonist exposure.

dc.contributor.author Bolanowski, MA
dc.contributor.author Bouvier, M
dc.contributor.author Caron, MG
dc.contributor.author Collins, Sheila
dc.contributor.author Lefkowitz, Robert J
dc.coverage.spatial United States
dc.date.accessioned 2013-09-24T17:35:39Z
dc.date.issued 1989-07
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/2472635
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10161/7867
dc.description.abstract In addition to conveying cellular responses to an effector molecule, receptors are often themselves regulated by their effectors. We have demonstrated that epinephrine modulates both the rate of transcription of the beta 2-adrenergic receptor (beta 2AR) gene and the steady-state level of beta 2AR mRNA in DDT1MF-2 cells. Short-term (30 min) exposure to epinephrine (100 nM) stimulates the rate of beta 2AR gene transcription, resulting in a 3- to 4-fold increase in steady-state beta 2AR mRNA levels. These effects are mimicked by 1 mM N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP) or foskolin but not by phorbol esters. The half-life of the beta 2AR mRNA after addition of actinomycin D (46.7 +/- 10.2 min; mean +/- SEM; n = 5) remained unchanged after 30 min of epinephrine treatment (46.8 +/- 10.6 min; mean +/- SEM; n = 4), indicating that a change in transcription rate is the predominant factor responsible for the increase of beta 2AR mRNA. Whereas brief exposure to epinephrine or Bt2cAMP does not significantly affect the total number of cellular beta 2ARs (assessed by ligand binding), continued exposure results in a gradual decline in beta 2AR number to approximately 20% (epinephrine) or approximately 45% (Bt2cAMP) of the levels in control cells by 24 hr. Similar decreases in agonist-stimulated adenylyl cyclase activity are observed. This loss of receptors with prolonged agonist exposure is accompanied by a 50% reduction in beta 2AR mRNA. Transfection of the beta 2AR promoter region cloned onto a reporter gene (bacterial chloramphenicol acetyltransferase) allowed demonstration of a 2- to 4-fold induction of transcription by agents that elevate cAMP levels, such as forskolin or phosphodiesterase inhibitors. These results establish the presence of elements within the proximal promoter region of the beta 2AR gene responsible for the transcriptional enhancing activity of cAMP and demonstrate that beta 2AR gene expression is regulated by a type of feedback mechanism involving the second messenger cAMP.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.subject 1-Methyl-3-isobutylxanthine
dc.subject Animals
dc.subject Base Sequence
dc.subject Cell Line
dc.subject Cell Membrane
dc.subject Colforsin
dc.subject Cricetinae
dc.subject Cyclic AMP
dc.subject Epinephrine
dc.subject Genes
dc.subject Glioma
dc.subject Kinetics
dc.subject RNA, Messenger
dc.subject Rats
dc.subject Receptors, Adrenergic, beta
dc.subject Tetradecanoylphorbol Acetate
dc.subject Theophylline
dc.subject Transcription, Genetic
dc.title cAMP stimulates transcription of the beta 2-adrenergic receptor gene in response to short-term agonist exposure.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/2472635
pubs.begin-page 4853
pubs.end-page 4857
pubs.issue 13
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Cell Biology
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Neurobiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 86


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