title: Differential effects of various phosphodiesterase inhibitors, pyrimidine and purine compounds, and inorganic phosphates on cyclic CMP, cyclic AMP and cyclic GMP phosphodiesterases.
abstract: The effects of various compounds on homogeneous cyclic CMP phosphodiesterase (cyclic CMP-PDE) from pig liver were compared with the effects on cyclic AMP phosphodiesterase (cyclic AMP-PDE) and cyclic GMP phosphodiesterase (cyclic GMP-PDE). Of the conventional inhibitors for AMP-PDE and cyclic GMP-PDE, only Sch 15280 was found to inhibit cyclic CMP-PDE. Nucleoside monophosphates, orthophosphate, and 2':3'-cyclic nucleotides were rather specific and were more effective in inhibiting cyclic CMP-PDE, compared to their effects on cyclic AMP-PDE and cyclic GMP-PDE. On the other hand, nucleoside di-and triphosphates and pyrophosphate (PPi) were less effective in inhibiting cyclic CMP-PDE and were without marked effect on cyclic AMP-PDE and cyclic GMP-PDE. Orthophosphate (Pi) was more potent than CMP, CDP and CTP in inhibiting cyclic CMP-PDE, with a rank order of inhibitory potency of Pi greater than CMP greater than CDP greater than CTP. Of the 3' :5'-cyclic nucleotides examined, cyclic UMP was more specific in inhibiting cyclic CMP-PDE compared to its effect on cyclic AMP-PDE and cyclic GMP-PDE. In all experiments similar results were obtained when either cyclic CMP or cyclic AMP was used as a substrate for this multifunctional cyclic CMP-PDE, supporting the contention that a single catalytic site on the enzyme is responsible for the hydrolysis of both cyclic CMP and cyclic AMP. The present studies further support our original suggestion that cyclic CMP-PDE is a unique enzyme that is distinguishable from the conventional enzymes for purine cyclic nucleotides.
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D006168:Guinea Pigs; D010710:Phosphates / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013552:Swine
chemical_list: D010710:Phosphates; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D011743:Pyrimidines; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase