Assessment of selective inhibition of rat cerebral cortical calcium-independent and calcium-dependent phosphodiesterases in crude extracts using deoxycyclic AMP and potassium ions

Biochim Biophys Acta. 1984 Mar 1;797(3):354-62. doi: 10.1016/0304-4165(84)90257-5.


The effects of various inhibitors on the activity of calcium-independent and calcium-dependent phosphodiesterases from rat cerebral cortex were examined. While the agents varied greatly in their relative potency, each was found to be approximately equipotent in inhibiting the calcium-dependent hydrolysis of either cyclic AMP or cyclic GMP. In contrast, the inhibitors displayed a marked substrate specificity for the calcium-independent enzyme with ratios of IC50 values for inhibition of cyclic GMP hydrolysis when compared to cyclic AMP hydrolysis in decreasing order being: ZK 62711 (much greater than 100) greater than Ro 20-1724 (much greater than 25) papaverine (13) greater than 7-benzyl IBMX (4) greater than quercetin and kaempferol (2). The differential selectivity of the inhibitors for the two enzymes was most pronounced for ZK 62711 and Ro 20-1724 which were at least 25-100-times more potent in inhibiting the calcium-independent hydrolysis of cyclic AMP when compared to the calcium-dependent hydrolysis of cyclic AMP. In contrast, 7-benzyl IBMX, kaempferol and quercetin were 8-100-times more effective as inhibitors of cyclic GMP hydrolysis by the calcium-dependent phosphodiesterase while 7-benzyl IBMX and trimazosin displayed a similar enzyme selectivity using cyclic AMP as substrate. With the exception of papaverine, all agents were competitive inhibitors of the calcium-dependent phosphodiesterase. The type of inhibition observed with the calcium-independent enzyme was dependent on the substrate employed. The specificity of potassium ions in inhibiting the activity of the calcium-dependent phosphodiesterase and deoxycyclic AMP in inhibiting the calcium-independent enzyme was found to provide a convenient means to assess the effects of agents on these activities in crude extracts of cerebral cortex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology*
  • Cyclic AMP / analogs & derivatives*
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cyclic GMP / metabolism
  • Female
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / metabolism*
  • Potassium / pharmacology*
  • Rats
  • Rats, Inbred Strains


  • Phosphodiesterase Inhibitors
  • 2'-deoxy cyclic AMP
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Cyclic GMP
  • Potassium
  • Calcium