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• W2040377097 abstract "During myocardial ischemia, a local release of noradrenaline coincides with an increased density of β-adrenergic receptors. The functional activity of these receptors, however, is mainly determined by their state of phosphorylation. The β-adrenergic receptor kinase (βARK) specifically phosphorylates and thereby inactivates β-adrenergic receptors after stimulation by receptor agonists, facilitating the binding of the inhibitor protein β-arrestin to the receptors. βARK activation involves a translocation of the enzyme to the membrane. In the present study, we investigated the density and the functional activity of β-adrenergic receptors, the enzymatic activity of βARK in membranes and cytosol, the mRNA levels of βARK-1, and the expression of β-arrestin during stop-flow and low-flow ischemia in the isolated perfused rat heart. After 60 minutes of stop-flow ischemia, β-adrenergic receptor density was upregulated, but β-agonist–mediated adenylate cyclase activity was blunted. Simultaneously, βARK activity in the particulate fraction was significantly induced. The increase in βARK activity was reversible after inhibition of ischemia-evoked noradrenaline release by desipramine. Also, exposure to externally given noradrenaline increased βARK activity in the particulate fraction. Cytosolic βARK activity remained largely unchanged during stop-flow or low-flow ischemia. The steady state concentration of βARK-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 β-arrestin levels. During myocardial ischemia, an increase in the number of β-adrenergic receptors is paralleled by increased membrane activity of the receptor kinase βARK. This increased membrane activity may contribute to enhanced receptor phosphorylation and inactivation." @default.
• W2040377097 created "2016-06-24" @default.
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• W2040377097 date "1996-09-01" @default.
• W2040377097 modified "2023-10-18" @default.
• W2040377097 title "Activation of β-Adrenergic Receptor Kinase During Myocardial Ischemia" @default.
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• W2040377097 doi "https://doi.org/10.1161/01.res.79.3.455" @default.
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