Effect of α‐Adrenergic Stimulation on Activation of Protein Kinase C and Phosphorylation of Proteins in Intact Rabbit Hearts
作者:
Laszlo Talosi,
Evangelia Kranias,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 70,
issue 4
页码: 670-678
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: α-adrenoceptors;protein kinase C;protein phosphorylation;heart
数据来源: OVID
摘要:
The intracellular events and specifically the role of protein kinase C-mediated protein phosphorylation, after α-adrenergic receptor stimulation of the heart, are not well understood. We examined the phosphorylation of sarcolemmal, sarcoplasmic reticular, myofibrillar, and cytosolic proteins in perfused beating rabbit hearts on activation of protein kinase C by phenylephrine. Perfusion of rabbit hearts with phenylephrine was associated with a positive inotropic response, which was dose and time dependent. Maximal stimulation (1.54-fold increase in +dP/dt) was obtained with 10 μM phenylephrine at 4 minutes. Examination of the activity levels of protein kinase C in these hearts revealed a redistribution of this activity from the cytosolic to the membranous fraction, suggesting the activation of this enzyme in vivo. Prazosin, an α1-adrenergic antagonist, prevented the increase in the inotropy and the redistribution of protein kinase C activity mediated by phenylephrine. Examination of the degree of phosphorylation of membranous, myofibrillar, and cytosolic proteins revealed that activation of protein kinase C in vivo was associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28-kd cytosolic protein. There were no increases in the degree of phosphorylation of phospholamban in the sarcoplasmic reticulum and of troponin I, troponin T, and C protein in the myofibrils, although these proteins were found to be substrates for protein kinase C in vitro. These findings provide evidence that protein kinase C is activated in response to α-adrenergic stimulation and that activation is associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28-kd cytosolic protein in the myocardium.
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