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.
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Schwabe, U., Ebert, R. & Erbler, H.C. Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3′,5′-AMP levels and lipolysis. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 133–148 (1973). https://doi.org/10.1007/BF00501186
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DOI: https://doi.org/10.1007/BF00501186