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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 30 (1973), S. 139-145 
    ISSN: 1432-0738
    Keywords: Paraoxone ; Obidoxime, HS 3, HS 6 ; Lipolysis ; Fat Cells ; Paraoxon ; Obidoxim, HS 3, HS 6 ; Lipolyse ; Fettzellen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im LD50-Bereich (10−7 - 10−5 M) beeinflußte Paraoxon dosisabhängig die Lipolyse isolierter Fettzellen aus dem Nebenhoden-Fettgewebe von Ratten. Die nicht kompetitive Hemmung der Glycerinfreisetzung wurde sowohl bei der basalen, als auch bei der durch 10−6 M Noradrenalin oder 3 × 10−3 M Dibutyryl-A-3′, 5′-MP stimulierten Lipolyse beobachtet (K1 = 1,1 × 10−6 M). HS 3, Obidoxim oder HS 6 hatten keinen Einfluß auf die durch 10−6 M Paraoxon bewirkte etwa 50 %ige Hemmung der maximal stimulierten Lipolyse. Weder eine Reaktivierung noch eine Direktwirkung zwischen Paraoxon und den geprüften Oximen war in diesem Testsystem nachweisbar.
    Notes: Abstract In experiments with isolated epididymal fat cells, paraoxone caused a dose-dependent inhibition of lipolysis in the LD50 dose range (10−7 - 10−5 M). The inhibition occurred in unstimulated as well as stimulated lipolysis elicited by 10−6 M norepinephrine or 3 × 10−3 M dibutyryl-A-3′, 5′-MP. The type of inhibition showed a noncompetitive pattern at an apparent Ki = 1.1 × 10−6 M. Obidoxime, HS 3 and HS 6 did not abolish the 50% inhibition of maximum lipolysis elicited by 10−6 M paraoxone. Neither a reactivation nor a direct interaction between paraoxone and oximes was observed in this test system.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 30 (1973), S. 175-182 
    ISSN: 1432-0738
    Keywords: Paraoxon ; Adenyl Cyclase ; ATP-Levels ; Phosphodiesterase ; Protein Kinase ; Fat Cells ; Paraoxon ; Adenylcyclase ; ATP-Gehalt ; Phosphodiesterase ; Proteinkinase ; Fettzellen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Paraoxon übt seine antilipolytische Wirkung auf das lipolytische System der Fettzelle durch einen direkten Einfluß auf die Triglyceridlipase aus. Es beeinflußt nicht andere Komponenten dieses Systems wie die Adenylcyclase, die Phosphodiesterase, den ATP-Gehalt der Zellen und die Bindungskapazität der cyclisch 3′,5′-AMP abhängigen Proteinkinase. Die durch diese Proteinkinase bewirkte Phosphorylierung von Protein wird ebenfalls nicht durch Paraoxon gehemmt. Somit erscheint die Fettzelle als geeignet, direkte Beeinflussung der esterasehemmenden Wirkung von Alkylphosphaten durch Antidote in einer lebenden Zelle zu erfassen.
    Notes: Abstract Paraoxon exerts its antilipolytic effect on the lipolytic system of fat cells by a direct interaction with the triglyceride lipase. It does not affect other components of the lipolytic system such as adenyl cyclase, phosphodiesterase, ATP-levels or binding of cyclic 3′,5′-AMP-dependent protein kinase. Phosphorylation of protein mediated by cyclic 3′,5′-AMP-dependent protein kinase is not impaired by paraoxon.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1977), S. 131-137 
    ISSN: 1432-1912
    Keywords: Glucocorticoids ; PGE release ; Cyclic AMP levels ; Glycosaminoglycan synthesis ; Fibroblast cultures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucocorticoids (GCs) reduced cyclic AMP levels and inhibited glycosaminoglycan (GAG) synthesis in secondary embryonic mouse fibroblast cultures, when cells were incubated for short periods (30 min). The order of potency was dexamethasone 〉 prednisolone 〉 hydrocortisone. The effect was more marked, when cyclic AMP levels and GAG synthesis were increased by addition of PGE1. Glucocorticoids exerted no longer an inhibitory effect on cyclic AMP and GAG synthesis in cultures pretreated for 48 h with the steroids. Addition of PGE1 caused a stronger rise in cyclic AMP and GAG synthesis than in controls without GC-preincubation. This enhancement was even more pronounced, when PGE1 was added together with the GCs. The reversal of the inhibitory effect of the GCs into a potentiating effect following preincubation correlated to a reduction of endogenous PGE formation in the cultures. Short-term treatment with GCs did not reduce endogenous PGE levels, but prolonged incubation markedly decreased PGE levels. PGE formation recovered following addition of fresh medium after the 48 h incubation with the steroids, but the amount of PGE formed remained significantly lower than in untreated cultures. Non-glucocorticoid steroid hormones did not decrease PGE levels. The results indicate that the apparent loss of inhibitory activity of GCs on cyclic AMP and GAG synthesis observed after prolonged incubation may result from a reduction of endogenous PGE formation which renders the cells more sensitive to the stimulatory effect of exogenous PGE1.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Lipolysis ; Adenyl Cyclase ; Phosphodiesterase ; Glucocorticoids ; Cyclic AMP ; Cortisone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of adrenalectomy and cortisone replacement in rats on the activities of adenyl cyclase and phosphodiesterase in homogenates of isolated fat cells and on the accumulation of cyclic 3′,5′-AMP in intact cells were studied. 1. Adrenalectomy caused a decrease in the activity of norepinephrine- and fluoride-stimulated adenyl cyclase in homogenates of isolated fat cells. This decrease was not significantly reversed by pretreatment of the animals with cortisone in vivo. 2. Adrenalectomy caused an increase in the activity of phosphodiesterase. This increase was not reversed by pretreatment of the animals with cortisone for 4 h in vivo but was reversed after 18 h. Incubation of cells from adrenalectomized animals with cortisone in vitro caused no change in phosphodiesterase activity. 3. The incorporation of prelabelled nucleotides into cyclic 3′,5′-AMP was significantly reduced in intact cells from adrenalectomized rats. Pretreatment of the animals with cortisone in vivo for 4 h completely restored the ability of the cells to accumulate radiolabelled cyclic 3′,5′-AMP upon stimulation by norepinephrine. The experiments underline the difficulties in comparing activation patterns of enzymes under optimal conditions with those occurring in the intact cell. The nature of the lesion in lipolysis caused by adrenalectomy and the reversal of this lesion by cortisone replacement can be demonstrated in the intact cell only.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 311 (1980), S. 67-70 
    ISSN: 1432-1912
    Keywords: PGI2, PGI analogues, PGE1 ; cAMP levels ; Isobutylmethylxanthine ; Cultured endothelial and smooth muscle cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary PGI2 increased cAMP levels in cultured endothelial cells derived from bovine aortas in the presence of isobutylmethylxanthine (IBMX). Stable PGI analogues were more effective, while PGE1 was without effect. In cultured smooth muscle cells from bovine aortas, PGI2, PGE1 and the stable PGI analogues dose-dependently increased cAMP levels in the absence and presence of IBMX. The data confirm the stimulatory effect of PGI2 on cAMP content in bovine coronary artery rings and suggest that the effect is mainly due to the stimulatory action of PGI2 on cAMP in smooth muscle cells.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 289 (1975), S. 29-40 
    ISSN: 1432-1912
    Keywords: cAMP ; Anti-Inflammatory Drugs ; Glycosaminoglycan Synthesis ; Fibroblasts ; Regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of non-steroidal anti-inflammatory drugs on formation and release of glycosaminoglycans (GAG) and cyclic 3′,5′-AMP levels was studied in embryonic mouse fibroblasts. The results were compared and correlated with the action of these drugs on cyclic 3′,5′-AMP-dependent as well as independent protein kinase obtained from bovine diaphragm. 1. Phenylbutazone dose-dependently decreased cyclic 3′,5′-AMP levels and GAG secretion both in unstimulated and PGE1 stimulated cells. 2. Indometacin decreased cyclic 3′,5′-AMP levels and GAG secretion only in cells with elevated cyclic 3′,5′-AMP levels after stimulation by PGE1. 3. Sodium salicylate decreased cyclic 3′,5′-AMP levels in the presence and absence of PGE1. However, GAG secretion was reduced only in cells with elevated cyclic 3′,5′-AMP levels, since the drug activated cyclic 3′,5′-AMP-independent protein kinase activity, thus presumably precluding changes in GAG formation at low levels of cyclic 3′,5′-AMP. 4. Mefenamic acid decreased cyclic 3′,5′-AMP levels in cells stimulated by PGE1, whereas GAG secretion was increased both in the absence and presence of PGE1. This increase in GAG secretion was closely correlated to an enhanced cyclic 3′,5′-AMP-dependent and independent protein kinase activity. The results indicate that non-steroidal anti-inflammatory drugs may exert their effects on GAG formation by interfering with cyclic 3′,5′-AMP formation or function.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 278 (1973), S. 293-300 
    ISSN: 1432-1912
    Keywords: Cyclic 3′,5′-AMP-Dependent Protein Kinase ; Lipolysis ; Antilipolytic Drugs ; Phenylbutazone ; Mefenamic Acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclic 3′,5′-AMP-dependent protein kinase activity is inhibited by phenylbutazone both in the presence and absence of the cyclic nucleotide. Mefenamic acid stimulates the activity of the enzyme up to 10−4 M, being less effective at higher concentrations. These findings closely correlate with the influence of both drugs on lipolysis. Other antilipolytic drugs such as benzydamine, adrenergic blocking agents, insulin, prostaglandin E1 or nicotinic acid do not affect the activity of cyclic 3′,5′-AMP-dependent protein kinase. The results indicate that only in a few cases the effect on protein kinase activity may be causal for the antilipolytic action of drugs.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 309 (1979), S. 59-64 
    ISSN: 1432-1912
    Keywords: Atherosclerotic plaque formation ; Dipyridamole in vivo ; ATP content ; cAMP content ; PGI2 ; Platelets ; Aortic tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rabbits receiving an atherogenic diet for 2 months, the ATP content of platelet rich plasma (PRP) and arterial tissue was significantly elevated as compared to normal rabbits. This increase in ATP levels of platelets from atherosclerotic rabbits was paralleled by higher basal as well as PGI2-induced cAMP levels. In arterial tissues, an increase was only obtained in PGI2-stimulated cAMP content. Treatment with dipyridamole (DPD) for 4 weeks resulted in a reduction of the ATP content in platelets and arterial tissue from atherosclerotic rabbits to values seen in normal animals. Again, the reduction of ATP content was reflected in a decrease of basal as well as PGI2-induced cAMP levels in platelets, whereas in arterial tissue a decrease was only obtained in PGI2-induced cAMP content. At the same time, DPD treatment enhanced atherosclerotic plaque formation in the aortic wall. The enhanced atherosclerotic plaque formation seen in DPD treated atherosclerotic rabbits may be linked to the inhibition of adenosine uptake, resulting in a decrease of the adenine nucleotide pools of arterial wall cells. The decrease also caused a reduction in PGI2-induced cAMP content. This effect may be linked to altered proliferative activity, since in many cell types, stimulation of cAMP levels results in reduced proliferation rates.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 274 (1972), S. 113-124 
    ISSN: 1432-1912
    Keywords: Adrenalectomy ; Cortisone ; Lipolysis ; Norepinephrine ; Fat Cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Studies on the norepinephrine-stimulated lipolytic system of rat epididymal fat tissue and fat cells revealed that adrenalectomy causes two lesions in the lipolytic system: 1. A decrease of the total amount of lipase available for activation by lipolytic agents acting via cyclic 3′,5′-AMP. This decrease cannot be reversed by short term pretreatment of the animals with cortisone in vivo. 2. An additional decrease of the lipolytic response to norepinephrine. This decrease can be reversed within 4 h by treatment of the animals with cortisone in vivo (“Permissive” effect).
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 293 (1976), S. 75-80 
    ISSN: 1432-1912
    Keywords: Dopaminergic stimulants ; Cyclic nucleotides ; Stereotyped behaviour ; Dose and time dependency ; Medial forebrain ; Cerebellum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dopaminergic stimulants (amantadine, amphetamine, apomorphine, nomifensine and L-dopa plus benserazide) increased cyclic GMP levels in the medial forebrain and cerebellum of mice. Cyclic AMP levels were not significantly altered under these conditions. Drug-induced stereotyped behaviour correlated in intensity and duration to the changes in cyclic GMP levels in the medial forebrain. Amantadine, apomorphine and nomifensine showed a linear dose response relationship, but differed as to the extent and time course of the increase in cyclic GMP. Amantadine and apomorphine were more effective in elevating cyclic GMP in the medial forebrain than in the cerebellum. Amphetamine produced an exponential dose-related elevation of cyclic GMP in both parts of the brain, being more effective in the cerebellum than in the medial forebrain at high doses, thus indicating a complex mechanism of action. L-Dopa (50 mg/kg) and benserazide (40 mg/kg) alone did neither significantly increase cyclic GMP levels nor induce stereotyped behaviour. However, in animals pretreated with benserazide (15 min prior to L-dopa) L-dopa produced a significant elevation of cyclic GMP and stereotyped behaviour.
    Type of Medium: Electronic Resource
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