title: 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 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 cyclic AMP phosphodiesterase (A-PDE) and cyclic GMP phosphodiesterase (G-PDE) activities. When assayed using 1 micron substrates, theophylline inhibited C-PDE to a lesser extent than A-PDE and G-PDE. 2'-Deoxy cyclic AMP (specific A-PDE inhibitor) and 2'-deoxy cyclic GMP (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, was without 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. The present findings suggest that C-PDE represents a potential site of specific pharmacological regulations, and that C-PDE may be a separate enzyme distinguishable from the purine cyclic nucleotide class of phosphodiesterases.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D010208:Papaverine / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013806:Theophylline / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D010710:Phosphates; D010726:Phosphodiesterase Inhibitors; C018892:2'-deoxy cyclic AMP; C018893:2'-deoxy cyclic GMP; D013806:Theophylline; D010208:Papaverine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine