Pharmacological inhibition of calmodulin-sensitive phosphodiesterases.

Two cyclic nucleotide phosphodiesterases sensitive to calmodulin were partially purified from bovine brain and bovine aorta. The enzyme from bovine brain exhibited the properties of the "high Km phosphodiesterase", with a higher Km for cyclic AMP than for cyclic GMP. The enzyme from bovine aorta hydrolyzed both cyclic AMP and cyclic GMP with similar kinetics. The hydrolysis of cyclic AMP by the brain enzyme was selectively inhibited by papaverine and 2' deoxy cyclic AMP. The hydrolysis of cyclic GMP by this enzyme was selectively inhibited by cyclic IMP, 2' deoxy cyclic GMP, 1-methyl-3-isobutyl-xanthine, ICI 74917 and M & B 22948. All these inhibitors were identically potent on the hydrolysis of both substrates by the aorta enzyme. Ro-20 1724, an imidazolidinone, and ZK 62711, a pyrrolidone, two compounds known to be potent inhibitors of cyclic AMP phosphodiesterase insensitive to calmodulin, were inefficient inhibitors of both calmodulin-sensitive phosphodiesterases.