EFFECTS OF PHOSPHODIESTERASE INHIBITORS, IMIDAZOLE AND PHOSPHATE ON CYCLIC CMP PHOSPHODIESTERASE ARE DIFFERENT FROM THOSE ON CYCLIC-AMP AND CYCLIC-GMP PHOSPHODIESTERASES

Abstract

The effects of various agents on the newly identified cyclic[c]CMP phosphodiesterase (C-PDE) in crude extracts of a number of rat tissues and on the enzyme partially purified from the rat liver were examined. Papaverine and 1-methyl-3-isobutylxanthine were without effects on C-PDE at concentrations that inhibited up to 90% of cAMP phosphodiesterase (A-PDE) and cGMP phosphodiesterase (G-PDE) activities. When assayed using 1 .mu.M substrates, theophylline inhibited C-PDE to a lesser extent than A-PDE and G-PDE. 2''-Deoxy cAMP (specific A-PDE inhibitor) and 2''-deoxy cGMP (specific G-PDE inhibitor) were relatively poor and non-specific inhibitors for C-PDE. Imidazole, while augmenting the high Km A-PDE and G-PDE from the liver but not from the heart, had no effect on the liver C-PDE but stimulated the heart C-PDE. Potassium phosphate was more specific in inhibiting C-PDE than A-PDE and G-PDE. Apparently C-PDE represents a potential site of specific pharmacological regulations. C-PDE may be a separate enzyme distinguishable from the purine cyclic nucleotide class of phosphodiesterases.