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Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.

dc.contributor.author Drazner, Mark H
dc.contributor.author Dyer, S
dc.contributor.author Grant, AO
dc.contributor.author Koch, Walter J
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Peppel, Karsten C
dc.coverage.spatial United States
dc.date.accessioned 2013-09-10T14:46:17Z
dc.date.issued 1997-01-15
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/9005997
dc.identifier.issn 0021-9738
dc.identifier.uri https://hdl.handle.net/10161/7831
dc.description.abstract Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either the human beta2-adrenergic receptor (beta2AR) or an inhibitor of the beta-adrenergic receptor kinase (betaARK), an enzyme that phosphorylates and uncouples agonist-bound receptors, have increased myocardial inotropy. We now have created recombinant adenoviruses encoding either the beta2AR (Adeno-beta2AR) or a peptide betaARK inhibitor (consisting of the carboxyl terminus of betaARK1, Adeno-betaARKct) and tested their ability to potentiate beta-adrenergic signaling in cultured adult rabbit ventricular myocytes. As assessed by radioligand binding, Adeno-beta2AR infection led to approximately 20-fold overexpression of beta-adrenergic receptors. Protein immunoblots demonstrated the presence of the Adeno-betaARKct transgene. Both transgenes significantly increased isoproterenol-stimulated cAMP as compared to myocytes infected with an adenovirus encoding beta-galactosidase (Adeno-betaGal) but did not affect the sarcolemmal adenylyl cyclase response to Forskolin or NaF. beta-Adrenergic agonist-induced desensitization was significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as compared to Adeno-betaGal-infected myocytes (37+/-1%, P < 0.001). We conclude that recombinant adenoviral gene transfer of the beta2AR or an inhibitor of betaARK-mediated desensitization can potentiate beta-adrenergic signaling.
dc.language eng
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI119157
dc.subject Adenoviridae
dc.subject Adenylyl Cyclases
dc.subject Adrenergic beta-Agonists
dc.subject Animals
dc.subject Cell Survival
dc.subject Cells, Cultured
dc.subject Cyclic AMP
dc.subject Gene Transfer Techniques
dc.subject Genetic Vectors
dc.subject Heart Ventricles
dc.subject Humans
dc.subject Isoproterenol
dc.subject Male
dc.subject Rabbits
dc.subject Receptors, Adrenergic, beta-2
dc.subject Sarcolemma
dc.subject Signal Transduction
dc.subject Transgenes
dc.title Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/9005997
pubs.begin-page 288
pubs.end-page 296
pubs.issue 2
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 99


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