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  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 297-306 
    ISSN: 1432-1912
    Keywords: cGMP ; cAMP ; Arecoline ; Cholinesterase Inhibitors ; Mouse Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In mice, Arecoline in vivo dose-dependently increased the cGMP concentrations of the cerebellum and the “cerebrum” (= parts of cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) without influencing the cAMP levels. The cholinesterase inhibitors paraoxon and physostigmine caused an elevation only in “cerebrum”, whereas the cGMP content of the cerebellum even decreased. Pretreatment with atropine prevented the rise in cGMP levels as well as the symptoms of cholinergic stimulation elicited by arecoline or paraoxon. Diazepam reduced cGMP levels below control values and blocked the effect of arecoline, while typical symptoms due to arecoline, e.g., tremor and salivation remained unaffected. The tripeptide prolyl-leucyl-glycinamide (MIF) had no effect on either cGMP values or the peripheral signs of cholinergic stimulation elicited by arecoline. The results show that elevation of cGMP in the central nervous system caused by cholinomimetic agents can be prevented not only by cholinolytics, blocking muscarinic receptors but also by influencing other mechanisms to be discussed.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 169-172 
    ISSN: 1432-1912
    Keywords: Naloxone ; Cyclic GMP ; Cerebellum ; GABA-ergic Antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Naloxone in high doses (60–240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5–10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Cyclic GMP ; Cyclic AMP ; Excitatory agents ; Diazepam ; Pentobarbital ; Tremor ; Mouse brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effects of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 295 (1976), S. 21-26 
    ISSN: 1432-1912
    Keywords: Cyclic GMP ; Dopaminergic stimulants ; Dopaminergic antagonists ; Atropine ; GABAergic agonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of dopaminergic stimulants on the cyclic GMP content in the medial forebrain and the cerebellum were studied in mice pretreated with dopaminergic antagonists, cholinolytics and agents enhancing GABAergic transmission. Low doses of butyrophenones (haloperidol and spiroperidol) inhibited the rise in cyclic GMP levels and the stereotyped behaviour induced by amphetamine, but were without effect on the same biochemical and behavioural changes elicited by apomorphine. Higher doses effectively blocked the rise in cyclic GMP levels and the stereotyped behaviour elicited by both drugs. These findings suggest that low doses of the dopaminergic antagonists may predominantly act by interfering with the release of dopamine from presynaptic stores, while high doses may act by blockade of the postsynaptic dopaminergic receptor. The rise in cerebellar cyclic GMP levels elicited by dopaminergic stimulants appears not to involve cholinergic transmission, since atropine did not block the effects of the dopaminergic stimulants. Enhancement of GABAergic transmission by diazepam or aminooxyacetic acid antagonized the rise in cerebellar cyclic GMP content induced by the dopaminergic stimulants, but was without effect on the cyclic GMP content in the medial forebrain. Cyclic AMP levels were not affected by any of the drugs in both parts of the brain.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 55-61 
    ISSN: 1432-1912
    Keywords: cGMP ; Method ; Protein-Binding Assay ; Rat Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A modification of the protein-binding assay for guanosine 3′,5′-monophosphate (Murad et al., 1971) is decribed yielding a substantial increase in sensitivity together with a more simplified procedure. The method employs a purified enzyme preparation from lobster tail muscle with a dissociation constant for cGMP of about 5 nM. The nucleotide-protein complex is separated from free cGMP by charcoal treatment. 0.05–0.1pmoles cGMP are detectable by this procedure. cGMP contents of seven discrete regions of rat brain were determined to show the usefullness of the described method.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1912
    Keywords: Clonidine ; Cyclic GMP ; Behavioural effects ; Adrenolytics ; Cholinolytics ; Dopaminergic stimulants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Low doses of clonidine (0.1 mg/kg) caused sedation in mice and decreased cyclic GMP content in the cerebellum, but not in the medial forebrain. High doses of clonidine (10.0 mg/kg) caused only a moderate and transient fall in cerebellar cyclic GMP content, the values returning to controls or above after 30 min, when behavioural excitation occurred. Phentolamine potentiated and prolonged the moderate reduction in cerebellar cyclic GMP content of the high dose of clonidine, at the same time counteracting the clonidine-induced behavioural effects. In reserpinized mice, the high dose of clonidine caused a marked rise of cyclic GMP content in both areas of the brain and produced massive behavioural excitation. These results indicate that high doses of clonidine stimulate central α-adrenergic receptors. The decrease in cyclic GMP content elicited by clonidine was prevented or even converted into an increase by pretreatment of the mice with cholinolytics. An increase in locomotor activity and intensified tremor was observed under these conditions. Clonidine antagonized the elevation of cyclic GMP content and the behavioural manifestations elicited by direct or indirect dopaminergic stimulation. These data suggest cholinomimetic properties of the drug. A direct cholinomimetic action can, however, not be attributed to the drug, since stimulators of central muscarinic receptors such as arecoline and oxotremorine increased cyclic GMP content in both areas of the brain.
    Type of Medium: Electronic Resource
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