%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 }