Effect of adenosine, adenosine analogues and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells

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Abstract
It has been suggested that adenosine may be a physiologically important modulator of lipolysis. In the present study it was found that adenosine inhibited lipolysis stimulated by low (0.03 μM) concentrations of noradrenaline (NA). Lipolysis stimulated by higher concentrations (0.3 and 3 μM) of NA was inhibited to a minor degree or not at all. Theophylline (1 mM)‐induced lipolysis was inhibited by adenosine (IC60˜ 10μM). Inhibition of theophylline‐induced lipolysis was tested for several analogues of adenosine. Some N6‐sub‐stituted adenosine analogues and 2‐Cl‐adenosine were more potent inhibitors. Adenine‐nucleotides (ATP, ADP, AMP) were about equipotent with adenosine. Several adenosine analogues, including its breakdown products were considerably less potent or ineffective. None of the analogues tested inhibited the action of adenosine. Dipyridamol, dilazep and papaverine, which inhibit the uptake of adenosine into cells, caused only a slight enhancement of the antilipolytic effect of adenosine. None of the analogues inhibited the effect of adenosine. It is concluded that adenosine can inhibit lipolysis due to low, “physiological” concentrations of noradrenaline and of low concentration of theophylline via an action on a receptor structure on the cell surface which exhibits structural specificity.

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