CA2-CALMODULIN-ACTIVATED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE FROM THESOLUBLE FRACTION OF HUMAN BRAIN - KINETIC-PROPERTIES AND EFFECTS OF THE ANTIDEPRESSANT PYRAZIDOLE AND ITS NITRO ANALOG ON THE ENZYME()

The kinetic characteristics of two forms of soluble Ca2+-calmodulin-ac tivated phosphodiesterase (I and II) from human brain are presented Bo th forms of the phosphodiesterase demonstrate a higher affinity for cG MP than for cAMP, but the difference in K(m) of phosphodiesterase II f or cAMP and cGMP are less pronounced For both forms of the enzyme, cGM P competitively inhibits hydrolysis of cAMP. Activation of phosphodies terase I by Ca2+-calmodulin is characterized by increasing V without a ny changes in K(m) for both substrates. With phosphodiesterase II, the Ca2+-calmodulin-dependent increase in V is accompanied by decreasing K(m) for cAMP and cGMP. Pyrazidole and nitropyrazidole inhibit Ca2+-ca lmodulin-induced activity without influencing the basal phosphodiester ase activity. The data exclude competition of either compound with the substrate and calmodulin for the catalytic site and the allosteric Ca 2+-calmodulin-specific site. The allosteric effect of these compounds on the activity of phosphodiesterase apparently involves a site in the enzyme molecule which is distinct from the calmodulin-binding site.