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Effects of adenosine derivatives on cAMP accumulation and lipolysis in rat adipocytes and on adenylate cyclase in adipocyte plasma membranes

  • Thomas Trost
  • Klaus Stock
Article

Summary

N6-monosubstituted adenosine (Ad)-derivatives and Ad-derivatives altered in the adenine-or ribose-moiety have been compared with Ad in their effects on noradrenaline (NA)-stimulated cAMP accumulation, on lipolysis stimulated by NA or theophylline (THEO) and on adenylate cyclase (AC) activity of adipocyte plasma membranes.

In isolated adipocytes about 0.01 μM Ad caused a 50% inhibition of cAMP accumulation stimulated maximally by 1μM NA. Depending upon the structure of substituent, the Ad-N6-derivatives were up to one order of magnitude either more or less active than Ad itself. 2-fluoro-Ad was nearly as active as Ad, whereas 2′,5′-dideoxy-Ad and 2′-deoxy-Ad were practically ineffective as inhibitors of NA-stimulated cAMP accumulation. All compounds showed the same order of potency relative to Ad, when tested against lipolysis stimulated maximally by 1 mM THEO or submaximally by 0.3 μM NA.

In adipocyte plasma membranes a 50% inhibition of AC activity stimulated by 10μM NA was observed at about 10 μM Ad. None of the N6-substituted derivatives had any effect on either basal or NA-stimulated AC activity, whereas 2′,5′-dideoxy-Ad proved to be about 40 times more potent than Ad. 2′-deoxy-Ad and 2-fluoro-Ad were nearly equipotent to Ad. Similar results were obtained, if AC was stimulated with 5′-guanylylimidodiphosphate or NaF. Neither the N6-derivatives nor THEO could reverse the inhibitory effect of Ad on AC in plasma membranes.

It is concluded, that different mechanisms are involved in the inhibitory effects of Ad on cAMP accumulation and lipolysis in intact cells and on AC activity of adipocyte plasma membranes.

Key words

Fat cell cAMP Lipolysis Adenosine derivatives Plasma membranes 

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Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Thomas Trost
    • 1
  • Klaus Stock
    • 1
  1. 1.Institut für Pharmakologie, Abteilung IIMedizinische Hochschule HannoverHannover 61Federal Republic of Germany

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