@article{oai:niigata-u.repo.nii.ac.jp:00006461,
 author = {Cai, Ji-Qun and Yoshida, Yutaka and Imai, Shoichi},
 issue = {3},
 journal = {Acta medica et biologica, Acta medica et biologica},
 month = {Sep},
 note = {Cyclic nucleotide phosphodiesterase (PDE) isozymes were separated from the soluble fraction of porcine aortic smooth muscle by DEAE-Sepharose Fast Flow ion exchange chromatography, and the effects of depogen (a theophilline-7 -acetice acid salt of drotaverine) on the isozymes were investigated in comparison with those of various selective or nonselective PDE inhibitors. Five PDE isozymes (Types I-V) were identified on the basis of their regulatory and kinetic properties and their sensitivities to selective PDE inhibitors. Type I (calmodulin-stimulated) preferentially hydrolyzed cGMP. The presence of Type II was demonstrated by a marked stimulation of activity by cGMP. Because of an insufficient amount of the isozyme and the unavailability of specific inhibitors, no further study of the Type II PDE was conducted. The Type III (cGMP-inhibited) and Type IV(cAMP-specific) isozymes preferentially hydrolyzed cAMP. The Type V PDE (cGMP-specific) hydrolyzed cGMP with a high selectivity. Depogen inhibited Types I, III and V PDE isozymes with potencies much weaker than selective inhibitors of each PDE isozyme as well as a nonselective PDE inhibitor, 3-isobutyl- 1-methylxanthine. In contrast, the inhibitory action of depogen was most potent toward Type IV PDE (IC_<50> =17μM), being more potent than that of RO20-1724, a Type IV-specific inhibitor (IC_<50>=32μM). Theophilline-7-acetic acid produces only a minimal inhibition while the inhibitory activities of drotaverine were very much like those of depogen. These results suggest that depogen is a selective inhibitor of Type IV PDE isozyme and that the inhibitory activity of depogen is mainly attributable to drotaverine.},
 pages = {127--134},
 title = {Effects of Depogen on Various Isozymes of Cyclic Nucleotide Phosphodiesterase Isolated from Porcine Aorta},
 volume = {43},
 year = {1995}
}