Inhibition of the cyclic AMP-adenylate cyclase system and of secretion by high concentrations of adenosine in the dog thyroid

Abstract

Adenosine inhibits cyclic AMP accumulation in stimulated slices and adenylate cyclase in acellular preparations of dog thyroid. The onset of this inhibition is rapid, requires relatively high adenosine concentrations (⩾ 10μm) and occurs with all activators tested (TSH, PGE 1, forskolin and cholera toxin). The manganous ion, which uncouples receptor and cyclase, enhances the inhibition by adenosine. The effect of 2′,5′-dideoxyadenosine, the high concentration of adenosine needed, the Mn 2+ effect and the lack of reversal by methylxanthines all suggest that this effect bears on the “P”-site, i.e. on the cyclase itself. Adenosine also inhibits thyroid secretion, which shows that its effect bears on the follicular cells. However the fact that cyclic AMP and DB cyclic AMP induced secretion are also reduced by adenosine suggests that adenosine also inhibits cyclic AMP action.