Characterization of two forms of cyclic nucelotide phosphodiesterase from rabbit heart

Two forms of phosphodiesterase (PDE), one capable of being activated by calcium ions (PDE-I) and the other activated by cyclic nucelotides (PDE-II), were isolated from rabbit heart and separated by ion-exchange chromatography. PDE-I and PDE-II were shown to differ in molecular weight, kinetic constants, and in sensitivity to a number of chemical agents. Neither phosphodiesterase form could be "transformed" into the other one with acetone, alcohol, Lubrol, sulfhydryl reagents, or by changes in pH, ionic strength, by repeated freezing and thawing, or limited proteolysis. These data, together with the analysis of the effects of Ca2+ and calmodulin on purified and crude preparations of PDE-I and PDE-II, give grounds for concluding that the two PDE forms are not produced in the process of enzyme purification but are actually inherent to the myocardium. Both PDE types have a higher affinity to 3',5'-cAMP than to 3',5'-cGMP and can be considered as calcium-regulated (PDE-I) and cyclic nucleotide-regulated (PDE-II) forms of the enzyme.