%0 Journal Article %1 Ungerer1993 %A Ungerer, M. %A Bohm, M. %A Elce, J. S. %A Erdmann, E. %A Lohse, M. J. %D 1993 %J Circulation %K *Cyclic AMP-Dependent Adult Aged Base Binding, Calcium/pharmacology Cardiac Cardiomyopathy, Chain Competitive Contraction/drug Coronary Data Dilated/metabolism Disease/metabolism Electric Female Forskolin/pharmacology Humans Isoproterenol/pharmacology Kinases Kinases/genetics/*metabolism Low/*metabolism/physiopathology Male Messenger/metabolism Middle Molecular Muscles/drug Myocardial Oligonucleotide Output, Papillary Polymerase Probes/genetics Protein RNA, Reaction Receptor Sequence Stimulation beta-Adrenergic beta/genetics/metabolism effects Adrenergic %N 2 %P 454-63 %T Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8381058 %V 87 %X BACKGROUND. In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK). METHODS AND RESULTS. We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters. CONCLUSIONS. In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.

@article{Ungerer1993, abstract = {BACKGROUND. In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK). METHODS AND RESULTS. We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters. CONCLUSIONS. In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Ungerer, M. and Bohm, M. and Elce, J. S. and Erdmann, E. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/25a5d78cbf13253176e4e5ab99302db2d/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {3ac63ad243a4aeb269e7f0b59d38b951}, intrahash = {5a5d78cbf13253176e4e5ab99302db2d}, issn = {0009-7322 (Print) 0009-7322 (Linking)}, journal = {Circulation}, keywords = {*Cyclic AMP-Dependent Adult Aged Base Binding, Calcium/pharmacology Cardiac Cardiomyopathy, Chain Competitive Contraction/drug Coronary Data Dilated/metabolism Disease/metabolism Electric Female Forskolin/pharmacology Humans Isoproterenol/pharmacology Kinases Kinases/genetics/*metabolism Low/*metabolism/physiopathology Male Messenger/metabolism Middle Molecular Muscles/drug Myocardial Oligonucleotide Output, Papillary Polymerase Probes/genetics Protein RNA, Reaction Receptor Sequence Stimulation beta-Adrenergic beta/genetics/metabolism effects Adrenergic}, month = Feb, note = {Ungerer, M Bohm, M Elce, J S Erdmann, E Lohse, M J In Vitro Research Support, Non-U.S. Gov't United states Circulation Circulation. 1993 Feb;87(2):454-63.}, number = 2, pages = {454-63}, shorttitle = {Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart}, timestamp = {2010-12-14T18:22:43.000+0100}, title = {Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8381058}, volume = 87, year = 1993 }