Activation of beta-adrenergic receptor kinase during myocardial ischemia
M. Ungerer, K. Kessebohm, K. Kronsbein, M. Lohse, и G. Richardt. Circ Res, 79 (3):
455-60(сентября 1996)Ungerer, M Kessebohm, K Kronsbein, K Lohse, M J Richardt, G In Vitro
Research Support, Non-U.S. Gov't United states Circulation research
Circ Res. 1996 Sep;79(3):455-60..
Аннотация
During myocardial ischemia, a local release of noradrenaline coincides
with an increased density of beta-adrenergic receptors. The functional
activity of these receptors, however, is mainly determined by their
state of phosphorylation. The beta-adrenergic receptor kinase (beta
ARK) specifically phosphorylates and thereby inactivates beta-adrenergic
receptors after stimulation by receptor agonists, facilitating the
binding of the inhibitor protein beta-arrestin to the receptors.
beta ARK activation involves a translocation of the enzyme to the
membrane. In the present study, we investigated the density and the
functional activity of beta-adrenergic receptors, the enzymatic activity
of beta ARK in membranes and cytosol, the mRNA levels of beta ARK-1,
and the expression of beta-arrestin during stop-flow and low-flow
ischemia in the isolated perfused rat heart. After 60 minutes of
stop-flow ischemia, beta-adrenergic receptor density was upregulated,
but beta-agonist-mediated adenylate cyclase activity was blunted.
Simultaneously, beta ARK activity in the particulate fraction was
significantly induced. The increase in beta ARK activity was reversible
after inhibition of ischemia-evoked noradrenaline release by desipramine.
Also, exposure to externally given noradrenaline increased beta ARK
activity in the particulate fraction. Cytosolic beta ARK activity
remained largely unchanged during stop-flow or low-flow ischemia.
The steady state concentration of beta ARK-1 mRNA increased after
20 minutes of stop-flow ischemia and then returned to baseline values
after another 20 minutes. Cardiac ischemia did not alter beta-arrestin
levels. During myocardial ischemia, an increase in the number of
beta-adrenergic receptors is paralleled by increased membrane activity
of the receptor kinase beta ARK. This increased membrane activity
may contribute to enhanced receptor phosphorylation and inactivation.
Ungerer, M Kessebohm, K Kronsbein, K Lohse, M J Richardt, G In Vitro
Research Support, Non-U.S. Gov't United states Circulation research
Circ Res. 1996 Sep;79(3):455-60.
%0 Journal Article
%1 Ungerer1996
%A Ungerer, M.
%A Kessebohm, K.
%A Kronsbein, K.
%A Lohse, M. J.
%A Richardt, G.
%D 1996
%J Circ Res
%K *Arrestins AMP-Dependent Animals Base Cyclic Data Eye Ischemia/*metabolism Kinases Kinases/genetics/*metabolism Male Messenger/metabolism Molecular Myocardial Probes Protein Proteins/metabolism RNA, Rats Receptor Sequence Wistar beta-Adrenergic beta/metabolism Adrenergic
%N 3
%P 455-60
%T Activation of beta-adrenergic receptor kinase during myocardial ischemia
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8781479
%V 79
%X During myocardial ischemia, a local release of noradrenaline coincides
with an increased density of beta-adrenergic receptors. The functional
activity of these receptors, however, is mainly determined by their
state of phosphorylation. The beta-adrenergic receptor kinase (beta
ARK) specifically phosphorylates and thereby inactivates beta-adrenergic
receptors after stimulation by receptor agonists, facilitating the
binding of the inhibitor protein beta-arrestin to the receptors.
beta ARK activation involves a translocation of the enzyme to the
membrane. In the present study, we investigated the density and the
functional activity of beta-adrenergic receptors, the enzymatic activity
of beta ARK in membranes and cytosol, the mRNA levels of beta ARK-1,
and the expression of beta-arrestin during stop-flow and low-flow
ischemia in the isolated perfused rat heart. After 60 minutes of
stop-flow ischemia, beta-adrenergic receptor density was upregulated,
but beta-agonist-mediated adenylate cyclase activity was blunted.
Simultaneously, beta ARK activity in the particulate fraction was
significantly induced. The increase in beta ARK activity was reversible
after inhibition of ischemia-evoked noradrenaline release by desipramine.
Also, exposure to externally given noradrenaline increased beta ARK
activity in the particulate fraction. Cytosolic beta ARK activity
remained largely unchanged during stop-flow or low-flow ischemia.
The steady state concentration of beta ARK-1 mRNA increased after
20 minutes of stop-flow ischemia and then returned to baseline values
after another 20 minutes. Cardiac ischemia did not alter beta-arrestin
levels. During myocardial ischemia, an increase in the number of
beta-adrenergic receptors is paralleled by increased membrane activity
of the receptor kinase beta ARK. This increased membrane activity
may contribute to enhanced receptor phosphorylation and inactivation.
@article{Ungerer1996,
abstract = {During myocardial ischemia, a local release of noradrenaline coincides
with an increased density of beta-adrenergic receptors. The functional
activity of these receptors, however, is mainly determined by their
state of phosphorylation. The beta-adrenergic receptor kinase (beta
ARK) specifically phosphorylates and thereby inactivates beta-adrenergic
receptors after stimulation by receptor agonists, facilitating the
binding of the inhibitor protein beta-arrestin to the receptors.
beta ARK activation involves a translocation of the enzyme to the
membrane. In the present study, we investigated the density and the
functional activity of beta-adrenergic receptors, the enzymatic activity
of beta ARK in membranes and cytosol, the mRNA levels of beta ARK-1,
and the expression of beta-arrestin during stop-flow and low-flow
ischemia in the isolated perfused rat heart. After 60 minutes of
stop-flow ischemia, beta-adrenergic receptor density was upregulated,
but beta-agonist-mediated adenylate cyclase activity was blunted.
Simultaneously, beta ARK activity in the particulate fraction was
significantly induced. The increase in beta ARK activity was reversible
after inhibition of ischemia-evoked noradrenaline release by desipramine.
Also, exposure to externally given noradrenaline increased beta ARK
activity in the particulate fraction. Cytosolic beta ARK activity
remained largely unchanged during stop-flow or low-flow ischemia.
The steady state concentration of beta ARK-1 mRNA increased after
20 minutes of stop-flow ischemia and then returned to baseline values
after another 20 minutes. Cardiac ischemia did not alter beta-arrestin
levels. During myocardial ischemia, an increase in the number of
beta-adrenergic receptors is paralleled by increased membrane activity
of the receptor kinase beta ARK. This increased membrane activity
may contribute to enhanced receptor phosphorylation and inactivation.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Ungerer, M. and Kessebohm, K. and Kronsbein, K. and Lohse, M. J. and Richardt, G.},
biburl = {https://www.bibsonomy.org/bibtex/29340d0f5add5e7524027c5c50bc3bbe7/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {132d001beb278279b997d4bcd6393852},
intrahash = {9340d0f5add5e7524027c5c50bc3bbe7},
issn = {0009-7330 (Print) 0009-7330 (Linking)},
journal = {Circ Res},
keywords = {*Arrestins AMP-Dependent Animals Base Cyclic Data Eye Ischemia/*metabolism Kinases Kinases/genetics/*metabolism Male Messenger/metabolism Molecular Myocardial Probes Protein Proteins/metabolism RNA, Rats Receptor Sequence Wistar beta-Adrenergic beta/metabolism Adrenergic},
month = Sep,
note = {Ungerer, M Kessebohm, K Kronsbein, K Lohse, M J Richardt, G In Vitro
Research Support, Non-U.S. Gov't United states Circulation research
Circ Res. 1996 Sep;79(3):455-60.},
number = 3,
pages = {455-60},
shorttitle = {Activation of beta-adrenergic receptor kinase during myocardial ischemia},
timestamp = {2010-12-14T18:22:57.000+0100},
title = {Activation of beta-adrenergic receptor kinase during myocardial ischemia},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8781479},
volume = 79,
year = 1996
}