Stimulation of Guanosine 3',5'-Monophosphate-Phosphodiesterase Activity by Adrenocorticotropic Hormone-Activated Increase of Guanosine 3',5'-Monophosphate in Isolated Adrenocortical Carcinoma Cells*

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Abstract
The decline of ACTH-stimulated c[cyclic]GMP to the basal level in isolated adrenocortical carcinoma 494 cells [a model system] was inhibited by cyclic phosphodiesterase inhibitors. In time-course experiments, the ACTH-induced level of cGMP preceded the activation of phosphodiesterase. Cells incubated with increasing concentrations of exogenous cGMP responded with a corresponding increase in the cGMP-phosphodiesterase activity. cAMP was 100-fold less effective than cGMP in the activation of cGMP-phosphodiesterase, indicating the nucleotide specificity of enzyme activation. The activation of cGMP-phosphodiesterase by ACTH-induced cGMP or exogenous cGMP was rapid. There was no activation of cAMP-phosphodiesterase by exogenous cAMP or cGMP. One mechanism by which isolated adrenocortical carcinoma cells regulate the ACTH-induced increase in cGMP may be the cyclic nucleotide control of the activity of its phosphodiesterase, thereby regulating cGMP degradation.

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