Alpha-adrenergic regulation of phosphoinositide metabolism and protein kinase C in isolated cardiac myocytes.
alpha 1-Adrenergic regulation of phosphoinositide metabolism and protein kinase C translocation was studied in isolated rat cardiac myocytes. Exposure of [3H]inositol-labeled myocytes to norepinephrine in the presence of propranolol caused a dose-dependent increase in [3H]inositol phosphates. Norepinephrine also increased the level of membrane-associated protein kinase C from approximately 10% of total activity to 18%, with a dose response similar to that for generation of inositol phosphates. Depolarization of myocytes with 30 mM KCl had no effect on inositol phosphates or membrane-associated protein kinase C but potentiated the effect of submaximal norepinephrine on both parameters. The potentiation of protein kinase C translocation was amplified when extracellular Ca2+ was increased to 4 mM, resulting in membrane association of one-third of the total cellular activity. These data show that activation of protein kinase C occurs during alpha 1-adrenergic stimulation of cardiac myocytes and that elevation of intracellular Ca2+ amplifies this effect at least in part through increased phosphoinositide metabolism.
Kaku
T
T
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224.
Lakatta
E
E
Filburn
C
C
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D003902:Detergents / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D017830:Octoxynol; D010716:Phosphatidylinositols / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003902:Detergents; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011092:Polyethylene Glycols; D007294:Inositol; D015759:Ionomycin; D017830:Octoxynol; D011493:Protein Kinase C; D002122:Calcium Chloride; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; D011224:Prazosin