Modulation of Cyclic AMP Metabolism by Glucocorticoids in PC18 Cells

Jeffrey D. Yingling, Lynn Z. Fuller, Brian A. Jackson

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Abstract: Glucocorticoids modulate signal transduction mechanisms in a number of cell systems. As the adrenal medulla is exposed to relatively high levels of adrenal cortical glucocorticoids in vivo, particularly during periods of stress, the aim of the present study was to determine whether glucocorticoids modulate cyclic AMP (cAMP) metabolism in an in vitro model of this system, the PC18 cell line. Dexamethasone significantly potentiated cAMP accumulation in response to the adenosine analogue N6‐R‐phenylisopropyl adenosine (PIA), and in response to forskolin. This effect was both time‐ and concentration‐dependent. Maximal potentiation was observed after 48 h of exposure to 1 µM dexamethasone. Corticosterone and to a lesser extent aldosterone also significantly potentiated PIA‐dependent cAMP accumulation. In contrast, estradiol, testosterone, and triiodothyronine had no potentiative effect. Potentiation could be eliminated by coincubation with the protein synthesis inhibitor cycloheximide. In the presence of Ro 20‐1724, a cAMP‐phosphodiesterase inhibitor, the degree of potentiation of both PIA‐ and forskolin‐dependent cAMP accumulation was significantly decreased by 50–60%. These data suggested that altered cAMP‐phosphodiesterase activity may be involved in this response. However, cytosolic and membrane‐bound low Km cAMP‐phosphodiesterase activity was unchanged in dexamethasone‐treated cells compared with controls. Similarly, there were no significant differences in basal, PIA‐, forskolin‐, or GTPγS‐stimulated adenylate cyclase activities between groups. These studies indicate that glucocorticoids can potentiate cAMP accumulation in intact PC18 cells. The mechanism underlying this potentiation is likely to be multifactorial, but may be due in part to decreased cAMP catabolism.

Original languageEnglish
Pages (from-to)1271-1276
Number of pages6
JournalJournal of Neurochemistry
Issue number4
StatePublished - Oct 1994


  • Adenylate cyclase
  • Adrenal medulla
  • Cyclic AMP‐phosphodiesterase
  • Dexamethasone
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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