Effects of Dexamethasone and Glucagon after Long-Term Exposure on Cyclic AMP Phosphodiesterase 4 in Cultured Rat Hepatocytes

Forsythia fruit (Forsythia suspensa Vahl (Oleaceae)) is a common component of Kampo medicines for treating the common cold, influenza, and allergies. The main polyphenolic compounds in the leaves of F. suspensa are pinoresinol β-d-glucoside, phillyrin and forsythiaside, and their levels are higher in the leaves of the plant than in the fruit. It is known that polyphenolic compounds stimulate lipid catabolism in the liver and suppress dyslipidemia, thereby attenuating diet-induced obesity and polyphenolic anti-oxidants might attenuate obesity in animals consuming high-fat diets. Recently, phillyrin was reported as a novel cyclic AMP phosphodiesterase 4 (PDE4) inhibitor derived from forsythia fruit. It was expected that the leaves of F. suspensa might display anti-obesity effects and serve as a health food material. In this review, we summarized our studies on the biological effects of forsythia leaves containing phillyrin and other polyphenolic compounds, particularly against obesity, atopic dermatitis, and influenza A virus infection, and its potential as a phytoestrogen.

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Cyclic AMP Phosphodiesterase-4 in Brain Tumor Biology: Immunochemical Analysis

Tumors of the Central Nervous System, Volume 4 ◽

10.1007/978-94-007-1706-0_13 ◽

2011 ◽

pp. 119-127

Author(s):

B. Mark Woerner ◽

Joshua B. Rubin

Keyword(s):

Brain Tumor ◽

Cyclic Amp ◽

Tumor Biology ◽

Immunochemical Analysis ◽

Phosphodiesterase 4 ◽

Cyclic Amp Phosphodiesterase

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Cyclic AMP Phosphodiesterase-4 in Brain Tumor Biology: Immunochemical Analysis

Methods of Cancer Diagnosis, Therapy, and Prognosis ◽

10.1007/978-90-481-8665-5_7 ◽

2010 ◽

pp. 71-82

Author(s):

B. Mark Woerner ◽

Joshua B. Rubin

Keyword(s):

Brain Tumor ◽

Cyclic Amp ◽

Tumor Biology ◽

Immunochemical Analysis ◽

Phosphodiesterase 4 ◽

Cyclic Amp Phosphodiesterase

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Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes

Biochemical Journal ◽

10.1042/bj2300525 ◽

1985 ◽

Vol 230 (2) ◽

pp. 525-534 ◽

Cited By ~ 40

Author(s):

R A Pittner ◽

R Fears ◽

D N Brindley

Keyword(s):

Neutral Lipids ◽

Relative Proportion ◽

Rat Hepatocytes ◽

Glycerol Phosphate ◽

Acyltransferase Activity ◽

Phosphatidate Phosphohydrolase ◽

Cultured Rat Hepatocytes ◽

Total Glycerol

Rat hepatocytes were incubated in monolayer culture for 8 h. Glucagon (10nM) increased the total phosphatidate phosphohydrolase activity by 1.7-fold. This effect was abolished by adding cycloheximide, actinomycin D or 500 pM-insulin to the incubations. The glucagon-induced increase was synergistic with that produced by an optimum concentration of 100 nM-dexamethasone. Theophylline (1mM) potentiated the effect of glucagon, but it did not affect the dexamethasone-induced increase in the phosphohydrolase activity. The relative proportion of the phosphohydrolase activity associated with membranes was decreased by glucagon when 0.15 mM-oleate was added 15 min before the end of the incubations to translocate the phosphohydrolase from the cytosol. This glucagon effect was not seen at 0.5 mM-oleate. Since glucagon also increased the total phosphohydrolase activity, the membrane-associated activity was maintained at 0.15 mM-oleate and was increased at 0.5 mM-oleate. This activity at both oleate concentrations was also increased in incubations that contained dexamethasone, particularly in the presence of glucagon. Insulin increased the relative proportion of phosphatidate phosphohydrolase that was associated with membranes at 0.15 mM-oleate, but not at 0.5 mM-oleate. It also decreased the absolute phosphohydrolase activity on the membranes at both oleate concentrations in incubations that also contained glucagon and dexamethasone. None of the hormonal combinations significantly altered the total glycerol phosphate acyltransferase activity. However, glucagon significantly increased the microsomal activities, and insulin had the opposite effect. Glucagon also decreased the mitochondrial acyltransferase activity. There was a highly significant correlation between the total phosphatidate phosphohydrolase activity and the synthesis of neutral lipids from glycerol phosphate and 0.5 mM-oleate in homogenates of cells from all of the hormonal combinations. Phosphatidate phosphohydrolase activity is increased in the long term by glucocorticoids and also by glucagon through cyclic AMP. In the short term, glucagon increases the concentration of fatty acid required to translocate the cytosolic reservoir of activity to the membranes on which phosphatidate is synthesized. Insulin opposes the combined actions of glucagon and glucocorticoids. The long-term events explain the large increases in the phosphohydrolase activity that occur in vivo in a variety of stress conditions. The expression of this activity depends on increases in the net availability of fatty acids and their CoA esters in the liver.

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Interactions of nuclear protein from cultured rat hepatocytes with the cyclic AMP responsive elements and the NF1-CTF site in the promotor of the rat phosphoenolpyruvate carboxykinase gene

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(05)81428-7 ◽

1991 ◽

Vol 181 (1) ◽

pp. 367-374 ◽

Cited By ~ 5

Author(s):

Bruno Christ ◽

Annegret Nath ◽

Kurt Jungermann

Keyword(s):

Cyclic Amp ◽

Phosphoenolpyruvate Carboxykinase ◽

Nuclear Protein ◽

Rat Hepatocytes ◽

Cultured Rat Hepatocytes ◽

Phosphoenolpyruvate Carboxykinase Gene

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Cross-talk between glucagon- and adenosine-mediated signalling systems in rat hepatocytes: effects on cyclic AMP-phosphodiesterase activity

Biochemical Journal ◽

10.1042/bj3120763 ◽

1995 ◽

Vol 312 (3) ◽

pp. 763-767 ◽

Cited By ~ 14

Author(s):

M Robles-Flores ◽

G Allende ◽

E Piña ◽

J A García-Sáinz

Keyword(s):

Cyclic Amp ◽

Pertussis Toxin ◽

Plasma Membranes ◽

Rat Hepatocytes ◽

Dependent Manner ◽

Phosphodiesterase Activity ◽

Cyclic Amp Phosphodiesterase ◽

Cyclic Amp Accumulation ◽

A1 Adenosine Receptors ◽

Dose Dependent

The effect of adenosine analogues on glucagon-stimulated cyclic AMP accumulation in rat hepatocytes was explored. N6-Cyclopentyladenosine (CPA), 5′-N-ethylcarboxamidoadenosine and N6-(R-phenylisopropyl)adenosine inhibited in a dose-dependent manner the cyclic AMP accumulation induced by glucagon. This effect seems to be mediated through A1 adenosine receptors. Pertussis toxin completely abolished the effect of CPA on glucagon-stimulated cyclic AMP accumulation in whole cells which suggested that a pertussis-toxin-sensitive G-protein was involved. On the other hand, this action of adenosine analogues on glucagon-induced cyclic AMP accumulation was reverted by the selective low-Km cyclic AMP-phosphodiesterase inhibitor Ro 20-1724. Analysis of cyclic AMP-phosphodiesterase activity in purified hepatocyte plasma membranes showed that glucagon in the presence of GTP inhibited basal PDE activity by 45% and that CPA reverted this inhibition in dose-dependent manner. In membranes derived from pertussis-toxin-treated rats, we observed no inhibition of cyclic AMP-phosphodiesterase activity by glucagon in the absence or presence of CPA. Our results indicate that in hepatocyte plasma membranes, stimulation of adenylate cyclase activity and inhibition of a low-Km cyclic AMP phosphodiesterase activity are co-ordinately regulated by glucagon, and that A1 adenosine receptors can inhibit glucagon-stimulated cyclic AMP accumulation by blocking glucagon's effect on phosphodiesterase activity.

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