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  • 1
    Electronic Resource
    Electronic Resource
    Studies on the antilipolytic effect of adenosine and related compounds in isolated fat cells (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 278 (1973), S. 247-259 
    Details
    ISSN: 1432-1912
    Keywords: Adenosine ; Nucleosides ; Dipyridamole ; Lipolysis ; Fat Cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Basal lipolysis in isolated fat cells of rats was increased by adenosine in a dose-dependent manner. Low concentrations of this nucleoside (1–10 μM) inhibited noradrenaline-induced glycerol production by about 50% and completely blocked the effect of theophylline on fat cells. Glycerol release, induced by dibutyryl cyclic AMP, was increased by 5 μM adenosine. Inosine, hypoxanthine, and xanthine had weaker antilipolytic properties, whereas adenine was virtually without effect. Although dipyridamole (20 μM) strongly decreased the uptake of adenosine into fat cells, it did not counteract the antilipolytic action of this nucleoside. Low concentrations of adenosine (0.1 μM), which by themselves were without any effect, greatly enhanced the effect of insulin on lipolysis. It is tentatively suggested that adenosine may be involved in the physiological control of lipolysis and that this nucleoside has its site of action on the cell membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500286
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  • 2
    Electronic Resource
    Electronic Resource
    Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3′,5′-AMP levels and lipolysis (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 133-148 
    Details
    ISSN: 1432-1912
    Keywords: Adenosine ; Cyclic AMP ; Lipolysis ; Fat Cell ; Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of lipolytic stimulants on cyclic AMP levels and glycerol production is strongly dependent on the concentration of fat cells in the incubation medium. After addition of noradrenaline cyclic AMP levels in diluted fat cell suspensions (20 000 cells/ml) reached 10 fold higher levels and declined much more slowly than in concentrated cell suspensions (100 000 cells/ml). An inhibitory substance appeared in the incubation medium which, after addition to a suspension of fresh fat cells caused a dose-dependent inhibition of hormone effects. The inhibitor was produced during preincubation periods of the fat cells and was removed by washing the cells with fresh medium. Purification of the medium by acid extraction, gel filtration, thin layer chromatography and the identification by gas chromatography showed that the inhibitor released represents adenosine. After incubation with adenosine deaminase the inhibitory activity of the medium disappeared. No inhibitory activity was obtained from the incubation medium by solvent extraction, a procedure which fully recovered added PGE2. Adenosine appeared in the medium after 5 min of incubation of fat cells and reached maximal levels (0.2 nmol/ml/105 cells) after 20 min. Noradrenaline (10 μM) did not stimulate the release of adenosine from fat cells. Addition of 0.01 to 0.1 μM of adenosine to fat cells effectively inhibited cyclic AMP accumulation and lipolysis induced by noradrenaline. Hence, a delayed rise and the secondary decline of cyclic AMP levels after hormonal stimulation can be accounted for by adenosine released from fat cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501186
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  • 3
    Electronic Resource
    Electronic Resource
    Stimulation of cyclic adenosine 3′,5′-monophosphate accumulation and lipolysis in fat cells by adenosine deaminase (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 33-44 
    Details
    ISSN: 1432-1912
    Keywords: Cyclic AMP ; Adenosine ; Lipolysis ; Fat Cell ; Adenosine Deaminase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The basal lipolytic activity of isolated fat cells of the rat was greatly enhanced in the presence of 0.01 to 30 μg adenosine deaminase (ADA) per ml. This effect was more pronounced in dilute (20000 cells/ml) than in concentrated cell suspensions (100000 cells/ml); this is possibly due to the presence, in the incubation medium, of a high concentration of inosine which is formed by the deamination of the large amounts of adenosine released from high concentrations of fat cells. Inosine, although less potent than adenosine as an antilipolytic agent, markedly inhibited ADA-induced lipolysis at concentrations between 10 to 100 μM. The lipolytic effect of ADA was identical with the stimulation of lipolysis by 1 μM noradrenaline or 1 mM theophylline, while 1 mM dibutyryl cyclic AMP yielded two-fold higher values. The effects of ADA and lipolytic agents at maximally stimulating concentrations were not additive. After 5 min of incubation maximally effective concentrations of ADA which were also maximal with respect to lipolysis caused a 3- to 6-fold elevation of cyclic AMP levels in fat cells. A similar increase was observed with maximally effective concentrations of theophylline, whereas noradrenaline produced a 100- to 200-fold elevation. This indicates that a small accumulation of cyclic AMP may be sufficient to trigger the full lipolytic response. Furthermore, ADA, like theophylline, acted synergistically with noradrenaline and prevented the fall of cyclic AMP levels during 30 min of incubation. Insulin (100 μU/ml) and nicotinic acid (0.1 μM) decreased cyclic AMP accumulation and glycerol production induced by ADA. The results support the hypothesis that adenosine is released from isolated fat cells and that this nucleoside may serve as an inhibitor of adenyl cyclase activity, thus regulating cyclic AMP-dependent processes in adipose tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647401
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  • 4
    Electronic Resource
    Electronic Resource
    Biphasic effect of 5′-guanylylimidodiphosphate on fat cell adenylate cyclase (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 286 (1974), S. 297-313 
    Details
    ISSN: 1432-1912
    Keywords: Adenylate Cyclase ; Cyclic AMP ; Nucleotides ; Fat Cell ; Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 5′-Guanylylimidodiphosphate (GMP-PNP) had a biphasic effect on basal adenylate cyclase activity of rat fat cell ghosts, being inhibitory and stimulatory while GTP was mainly inhibitory. At low concentrations of GMP-PNP a transient inhibitory phase preceded the onset of activation. This initial inhibition was overcome by higher concentrations of GMP-PNP, ATP or magnesium. The stimulatory effects of GMP-PNP were increased by high concentrations of ATP or magnesium, the apparent K m for activation being a function of time. After 5 min of incubation half-maximal activation was obtained at 3 μM GMP-PNP, after 20 min of incubation the K m for GMP-PNP was found to be between 0.1 and 0.3 μM. After 20 min of incubation a 15fold increase of cyclase activity above basal level was observed in the presence of 1 μM GMP-PNP. GTP competitively inhibited the stimulant effect of GMP-PNP. On the other hand, it activated basal activity only under carefully selected conditions. GMP-PNP and noradrenaline had a synergistic action on cyclase activity. At high substrate concentrations (1 mM ATP) GMP-PNP shifted the apparent K m for activation by noradrenaline from 3 μM to 0.1 μM. At low substrate and high magnesium concentrations 1 μM noradrenaline was unable to stimulate adenylate cyclase. Under these conditions GMP-PNP facilitated the stimulation by the hormone, although GMP-PNP itself inhibited basal activity. It is suggested that GMP-PNP activates the adenylate cyclase by competing at a common nucleotide binding site with inhibitory agents such as free ATP or GTP. Moreover, the guanyl nucleotide analogue may initiate conformational changes of the enzyme system which facilitate the response to hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498312
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