[Ca2+-calmodulin-activated cyclic nucleotide phosphodiesterase from the soluble fraction of the human brain: Kinetic properties and the effect of the antidepressant pyrazidol and its nitro analog on the enzyme].

The kinetic characteristics of two forms of soluble Ca(2+)-calmodulin-activated phosphodiesterase (PDE I and PDE II) from human brain are presented. Both PDE forms display a higher affinity for cGMP than for cAMP: the differences in the Km values of PDE II for the both cyclic nucleotides are less pronounced. For the both enzyme forms cGMP competitively inhibits cAMP hydrolysis. Activation of PDE I by Ca(2+)-calmodulin is characterized by increasing Vmax without any changes in Km for both substrates. In case of PDE II the Ca(2+)-calmodulin-dependent increase in Vmax is accompanied by decreasing Km for cAMP and cGMP. Pyrazidol and nitropyrazidol inhibit Ca(2+)-calmodulin induced activity with no effect on basal PDE activity. The data obtained exclude competition of the both compounds with the substrate and the activator for the catalytic site and the allosteric Ca(2+)-calmodulin-specific site. It is suggested that the allosteric effect of these compounds on the activity of PDE involves a site in the enzyme which is distinct from the calmodulin-binding site.