An activator of protein kinase C (phorbol-12-myristate-13-acetate) augments 2-chloroadenosine-elicited accumulation of cyclic AMP in guinea pig cerebral cortical particulate preparations

FEBS Lett. 1985 May 20;184(2):339-42. doi: 10.1016/0014-5793(85)80634-7.


Norepinephrine and histamine markedly augment accumulations of cyclic AMP elicited by 2-chloroadenosine in a guinea pig cerebral cortical vesicular preparation. In addition, these biogenic amines stimulate phosphatidylinositol turnover. Phosphatidylinositol turnover is associated with mobilization of internal calcium and with stimulation of protein kinase C. Phorbol-12-myristate-13-acetate (PMA), a known activator of protein kinase C, has no effect on cyclic AMP levels alone, but in a concentration-dependent manner enhances accumulations of cyclic AMP elicited by 2-chloroadenosine. PMA, like norepinephrine, also enhances accumulations of cyclic AMP elicited by histamine. PMA has no effect on the synergistic accumulations of cyclic AMP elicited by combinations of amines and 2-chloroadenosine. PMA also augments accumulations of cyclic AMP elicited by forskolin. The results suggest that activation of phosphatidylinositol turnover by biogenic amines may lead via stimulation of protein kinase C to enhanced responsiveness of cyclic AMP-generating systems.

MeSH terms

  • 2-Chloroadenosine
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Animals
  • Cell-Free System
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cyclic AMP / metabolism*
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Guinea Pigs
  • Inositol Phosphates / metabolism
  • Male
  • Phorbols / pharmacology*
  • Protein Kinase C
  • Protein Kinases / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology*


  • Inositol Phosphates
  • Phorbols
  • 2-Chloroadenosine
  • Cyclic AMP
  • Protein Kinases
  • Protein Kinase C
  • Adenosine
  • Tetradecanoylphorbol Acetate