EFFECTS OF SATERINONE AND ITS ENANTIOMERS R(-SATERINONE ACID S(-)-SATERINONE ON THE PHOSPHODIESTERASE ISOENZYMES FROM VENTRICULAR TISSUE OFFAILING HUMAN HEARTS AND PORCINE HEARTS())

Stereoisomers often exhibit differences in their pharmacological activ ities. Therefore, the phosphodiesterase inhibitory effects of the card iotonic agent saterinone in form of the racemate were investigated in comparison with the inhibitory properties of its enantiomers R(+)- and S(-)-saterinone. For this purpose the phosphodiesterase isoenzymes fr om ventricular tissue of failing human hearts and porcine hearts were separated by DEAE-sepharose anion exchange chromatography. Four differ ent phosphodiesterase isoenzymes were isolated from failing human myoc ardium and designated phosphodiesterase I-IV. Three phosphodiesterase isoenzymes could be separated from ventricular tissue of porcine heart s. A Ca2+/calmodulin stimulated phosphodiesterase I was not detectable in porcine myocardium. In failing human hearts racemic saterinone was a potent inhibitor of phosphodiesterase III (IC50 0.02 mu mol/l) and IV (IC50 0.03 mu mol/l) as compared to the inhibition of phosphodieste rase I (IC50 37.3 mu mol/l) and II (IC50 51.4 mu mol/l). In comparison with the racemate, R(+)- and S(-)-saterinone showed only slight diffe rences in their phosphodiesterase inhibitory effects. R(+)-saterinone inhibited phosphodiesterase III slightly but significantly more potent ly and selectively than did S(-)-saterinone, Compared to the inhibitio n of phosphodiesterase I and II both enantiomers were similarly potent and selective inhibitors of phosphodiesterase III and IV. Similar res ults were obtained in porcine hearts. It is concluded that the racemat e saterinone and its enantiomers R(+)- and S(-)-saterinone are virtual ly equipotent concerning the inhibition of phosphodiesterase isoenzyme s isolated from failing human hearts or porcine ventricular tissue. Th e enantiomers of saterinone did not exhibit distinct stereoselectivity in their phosphodiesterase inhibitory effects.