Adrenergic activation of glycogen phosphorylase in primary culture diabetic cardiomyocytes

The basis of catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation that was apparent 3 h after cell isolation and was further enhanced on maintenance of the myocytes in culture for 24 h. Normal cells initially lacked the hypersensitive response to epinephrine stimulation, although on maintenance of these cells in culture for 24 h, the hypersensitive response was acquired in vitro. To assess alpha- and beta-adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a beta-blocker, before direct alpha 1-receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3- or 24-h cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol, whereas prazosin, an alpha-blocker, was unsuccessful. The present data suggest that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through beta-adrenergic receptor activation.

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Activation and distribution of rat parotid cAMP-dependent protein kinase following beta-adrenergic receptor stimulation in vitro

Archives of Oral Biology ◽

10.1016/0003-9969(89)90042-3 ◽

1989 ◽

Vol 34 (1) ◽

pp. 23-26 ◽

Cited By ~ 8

Author(s):

D.O. Quissell ◽

L.M. Deisher ◽

K.A. Barzen

Keyword(s):

Protein Kinase ◽

Adrenergic Receptor ◽

Beta Adrenergic Receptor ◽

Receptor Stimulation ◽

Dependent Protein Kinase ◽

Beta Adrenergic ◽

Camp Dependent Protein Kinase ◽

Dependent Protein ◽

Rat Parotid

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Hypertrophy of isolated adult feline heart cells following beta-adrenergic-induced beating

AJP Cell Physiology ◽

10.1152/ajpcell.1991.261.3.c530 ◽

1991 ◽

Vol 261 (3) ◽

pp. C530-C542 ◽

Cited By ~ 41

Author(s):

W. A. Clark ◽

S. J. Rudnick ◽

J. J. LaPres ◽

M. Lesch ◽

R. S. Decker

Keyword(s):

Cell Structure ◽

Cell Number ◽

High Yield ◽

Cardiomyocyte Hypertrophy ◽

Heart Cells ◽

Beta Adrenergic ◽

Adult Rat ◽

Beta Adrenergic Agonists ◽

Adrenergic Activation

Catecholamine-induced beating and myocardial hypertrophy were evaluated in isolated adult feline cardiomyocytes maintained in culture for up to 30 days. Adult feline cardiomyocytes were used in this study because they displayed several unique characteristics that facilitated assessment of factors regulating cardiomyocyte hypertrophy in vitro. These characteristics included the following. 1) A single heart provides a high yield of 20-40 x 10(6) calcium-tolerant rod-shaped myocytes. 2) In culture, isolated adult feline cardiomyocytes maintain a stable population of differentiated myocytes that could be maintained without the dramatic loss of cell number, DNA content, or cell structure seen in adult rat cardiomyocyte cultures. 3) Cultured feline cardiomyocytes remained quiescent in culture unless appropriately stimulated to begin beating. 4) Sustained regular beating activity could be readily initiated up to 3 wk in culture by addition of 1 x 10(-5) M isoproterenol, other beta-adrenergic agonists, or agents known to elevate adenosine 3',5'-cyclic monophosphate. Beating could be maintained indefinitely in the presence of isoproterenol, but ceased upon removal of isoproterenol from the medium. Initiation of beating in 7-day-old cultures resulted in a profound restructuring of cardiomyocyte morphology compared with quiescent cultures. Beating heart cells were 66% larger with increased protein content, and they had significantly greater development of striated myofibrillar structure than quiescent myocytes at the same age in culture. We conclude that maintenance of an organized myofibrillar structure in cultured adult cardiac myocytes requires activation of intrinsic beating. Cardiomyocyte hypertrophy also develops following beta-adrenergic activation of beating, but it is unclear whether beating per se is required for inducing hypertrophy in isolated adult cardiomyocytes in vitro.

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Modulation of myosin phosphatase targeting subunit and protein phosphatase 1 in the heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00318.2004 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1736-H1743 ◽

Cited By ~ 28

Author(s):

Ravi Rajashree ◽

Bradford C. Blunt ◽

Polly A. Hofmann

Keyword(s):

Protein Phosphatase ◽

Adrenergic Receptor ◽

Ventricular Myocytes ◽

Regional Distribution ◽

Rho Kinase ◽

Receptor Activation ◽

Spatial Gradient ◽

Receptor Stimulation ◽

Adult Rat ◽

Myosin Light Chain 2

Myosin light chain 2 (LC2) phosphorylation is of both physiological and pathological importance to myocardial function. The phosphatase that directly dephosphorylates LC2 is a type 1 protein phosphatase (PP1) that contains a catalytic subunit that complexes with a myosin-binding phosphatase targeting subunit (MYPT). The goal of the present study was to examine the role of MYPT in the regulation of PP1 in ventricular myocytes. In the first part of the study, regional distribution of MYPT expression and phosphorylation were determined in unstimulated hearts. The pattern of MYPT phosphorylation was inversely related to the LC2 phosphorylation spatial gradient as described by Epstein and colleagues (Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, and Epstein ND. Cell 107: 631–641, 2001). In the second part of the study, adult rat isolated ventricular myocytes were exposed to an α-adrenergic receptor agonist, and properties of MYPT, PP1, and LC2 were studied. We found MYPT associates with cardiac myofilaments, and this association increases upon α-adrenergic receptor stimulation. Activation of α-adrenergic receptors also led to a decrease in the PP1-myofilament association. Furthermore, α-adrenergic receptor stimulation results in phosphorylation of MYPT and LC2 and an increase in myocyte Ca2+ sensitivity of tension that all depend on Rho kinase activation. These data support the hypothesis that α-adrenergic receptor activation works through Rho kinase to phosphorylate MYPT, and phosphorylated MYPT dissociates from PP1 so that PP1 is no longer physically associated with LC2. Hence, we propose a pathway for the dynamic modulation of LC2 phosphorylation through receptor-dependent phosphorylation of MYPT, and a spatial gradient of LC2 phosphorylation under basal conditions that occurs due to varied levels of phosphorylation of MYPT in ventricles.

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Effects of adrenalectomy on binding to and actions of adrenergic receptors

Biochemical Journal ◽

10.1042/bj2370527 ◽

1986 ◽

Vol 237 (2) ◽

pp. 527-531 ◽

Cited By ~ 7

Author(s):

M F el-Refai ◽

T M Chan

Keyword(s):

Cyclic Amp ◽

Binding Sites ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Glycogen Phosphorylase ◽

Beta Adrenergic ◽

Cyclic Amp Accumulation ◽

Adrenergic Antagonists ◽

Adrenergic Activation ◽

Adrenalectomized Rats

Adrenalectomy results in significant changes in the mechanism of adrenergic activation of hepatic glycogenolysis. In adrenalectomized rats a greater role for the beta-adrenergic receptor is observed, whereas the alpha 1-adrenergic-mediated phosphorylase activation declines. Our present findings document that adrenalectomy causes a significant decrease in the high-affinity population of the alpha 1-adrenergic receptor labelled with [3H]adrenaline. Our data indicate a large increase in the number of beta-adrenergic binding sites after adrenalectomy. This increase was not consistent with the observed modest increase in the beta-adrenergic-mediated activation of cyclic AMP accumulation and glycogen phosphorylase. When alpha-adrenergic antagonists are present along with the catecholamine, a 100% increase in the adrenaline-mediated accumulation of cyclic AMP in hepatocytes from adrenalectomized rats was observed. Adrenalectomy was also shown to cause a significant increase in the hepatic alpha 2-adrenergic binding sites. These data are consistent with an inhibitory role on the beta-adrenergic-mediated activation of glycogenolysis by the hepatic alpha 2-adrenergic receptor in adrenalectomy.

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α1-Adrenergic receptor stimulation attenuates the voltage dependent Ca2+ influx in adult rat cardiomyocytes

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)57437-6 ◽

1988 ◽

Vol 46 ◽

pp. 199

Author(s):

Katsuomi Iwakura ◽

Yasuhiro Watanabe ◽

Toshihumi Kagiya ◽

Masatsugu Hori ◽

Takenobu Kamada ◽

...

Keyword(s):

Adrenergic Receptor ◽

Receptor Stimulation ◽

Rat Cardiomyocytes ◽

Adult Rat ◽

Voltage Dependent

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Control of glycogen synthase by insulin and isoproterenol in rat adipocytes. Changes in the distribution of phosphate in the synthase subunit in response to insulin and beta-adrenergic receptor activation.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)36145-8 ◽

1986 ◽

Vol 261 (2) ◽

pp. 669-677 ◽

Cited By ~ 1

Author(s):

J C Lawrence ◽

C James ◽

J F Hiken

Keyword(s):

Adrenergic Receptor ◽

Glycogen Synthase ◽

Receptor Activation ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Rat Adipocytes

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Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity

European Journal of Histochemistry ◽

10.4081/ejh.2012.15 ◽

2012 ◽

Vol 56 (2) ◽

pp. 15 ◽

Cited By ~ 6

Author(s):

M. Chiusa ◽

F. Timolati ◽

J.C. Perriard ◽

T.M. Suter ◽

C. Zuppinger

Keyword(s):

Cell Death ◽

Sodium Nitroprusside ◽

Rat Cardiomyocytes ◽

Adult Rat

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Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex

Journal of Thyroid Research ◽

10.1155/2013/457953 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Pradip K. Sarkar ◽

Avijit Biswas ◽

Arun K. Ray ◽

Joseph V. Martin

Keyword(s):

Cerebral Cortex ◽

Atpase Activity ◽

Adrenergic Receptor ◽

Receptor Activation ◽

Mammalian Brain ◽

Neuronal Membrane ◽

Dependent Manner ◽

Adrenergic Agonist ◽

Adult Rat ◽

Dose Dependent

The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3and theβ-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, theβ-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3on synaptosomal Na+-K+-ATPase activity was independent ofβ-adrenergic receptor activation. The effect of T3on synaptosomal Na+-K+-ATPase activity was inhibited by theα2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activateGi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

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