Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic
receptors in the failing human heart
M. Ungerer, M. Bohm, J. Elce, E. Erdmann, и M. Lohse. Circulation, 87 (2):
454-63(февраля 1993)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..
Аннотация
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.
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.
%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
}