Inhibition by adenosine of ACTH-stimulated adenylate cyclase and steroidogenesis in the adrenal cortex.

Effects of adenosine analogs on ACTH-stimulated adenylate cyclase activity and steroidogenesis in rat adrenocortical glands have been studied. Adenosine analogs inhibited ACTH-stimulated adenylate cyclase activity by a GTP-dependent process. Methylxanthines reversed the inhibitory effect of N6-phenyl-isopropyl-adenosine (PIA), but not of 2',5'-dideoxy-adenosine. These results suggest that adenosine negatively regulates the stimulation of adenylate cyclase by ACTH at the external and the internal site of the membrane. The inhibitory effect of PIA on ACTH-stimulated steroidogenesis by isolated cells was antagonized by methylxanthines. PIA also inhibited steroidogenesis induced by dibutyryl cAMP, suggesting an inhibitory action of the nucleoside distal to the cAMP system. These results suggest the presence of a common site located in the external membrane for adenosine which subsequently mediates two independent processes, one is negatively coupled to the adenylate cyclase and the other to steroidogenesis for negative feedback controls of the adrenal cortex.