Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases

Human, dog and rabbit corpus cavernosum type 5 phosphodiesterases (PDE5) we re isolated and their characteristics were compared. The three enzymes show ed Km values of 0.8, 2.1 and 2.3 uM, respectively. They exhibited similar p H-dependence with optimal pH being 7.5. They required Mg++ for activity and the activity was suppressed by high concentrations of Zn++ (0.1-1 mM). Sil denafil potently inhibited the three enzymes with ICS, values of 3.6, 1.7 a nd 3.0 nM, respectively. Dipyridamole and IBMX (3-isobutyl-1-methylxanthine ) each also inhibited the three enzymes with similar, albeit lower, potenci es (IC50 about 1.1 and 5.7 uM, respectively). However, zaprinast exhibited a significantly higher potency against the rabbit enzyme (IC50 53 nM) than against the human and dog PDE5s (IC50 332 and 217 nM, respectively). Thus, the corpus cavernosum PDE5s are very similar among the various species with the only significant difference being their sensitivity to zaprinast. Huma n platelet PDE5 was also characterized by comparison with the corpus cavern osum enzyme. The platelet enzyme exhibited a Km, pH-, Mg++- and Zn++-depend ence, and sensitivity to sildenafil and zaprinast very similar to those of the corpus cavernosum PDE5. However, compared with corpus cavernosum PDE5, the platelet enzyme exhibited higher sensitivity to dipyridamole and IBMX ( IC50 0.46 and 1.8 uM, respectively). This study shows that despite similar kinetics and enzymatic properties, corpus cavernosum PDE5s from different s pecies, and corpus cavernosum and platelet PDE5s, can have differential sen sitivity to pharmacological inhibitors. (C) 2001 Elsevier Science Inc. All rights reserved.