Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.
作者： M H Drazner , K C Peppel , S Dyer , A O Grant , W J Koch
DOI: 10.1172/JCI119157
关键词: Adrenergic receptor 、 Molecular biology 、 Myocyte 、 Adenoviridae 、 Signal transduction 、 Adenylyl cyclase 、 Forskolin 、 Transgene 、 Receptor 、 Biology
摘要: Our laboratory has been testing the hypothesis that genetic modulation of beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown transgenic mice with overexpression either human beta2-adrenergic receptor (beta2AR) or an inhibitor kinase (betaARK), enzyme phosphorylates and uncouples agonist-bound receptors, increased myocardial inotropy. now created recombinant adenoviruses encoding beta2AR (Adeno-beta2AR) a peptide betaARK (consisting carboxyl terminus betaARK1, Adeno-betaARKct) tested their ability to potentiate in cultured adult rabbit ventricular myocytes. As assessed by radioligand binding, Adeno-beta2AR infection led approximately 20-fold receptors. Protein immunoblots demonstrated presence Adeno-betaARKct transgene. Both transgenes significantly isoproterenol-stimulated cAMP as compared myocytes infected adenovirus beta-galactosidase (Adeno-betaGal) but did not affect sarcolemmal adenylyl cyclase response Forskolin NaF. beta-Adrenergic agonist-induced desensitization was inhibited Adeno-betaARKct-infected (16+/-2%) Adeno-betaGal-infected (37+/-1%, P < 0.001). conclude adenoviral gene transfer betaARK-mediated signaling.
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