CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE IN HUMAN CAVERNOUS SMOOTH-MUSCLE

Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophospha te (cGMP) are important second messengers in mediating relaxation of v arious smooth-muscle cells. This second-messenger pathway also appears to be essential for cavernous smooth-muscle relaxation on the basis o f the assumption it would be of theoretical and clinical interest to d etermine the functional relevance of various phosphodiesterase (PDE) i soenzymes in human cavernous smooth-muscle. This study was concentrate d on characterizing PDE isoenzymes that exist in cavernous smooth musc le and evaluating the effect of selective PDE inhibitors on relaxation that is needed for the initiation of erection. Separation of PDE isoe nzymes was performed using anion-exchange chromatography [diethylamino ethanol (DEAE)-Sepharose column], and a modification of the PDE-assay method proposed by Thompson and Lakey was used. The relaxation effect of PDE inhibitors was evaluated in an organ-bath study. Three differen t PDE isoenzymes have been shown in human cavernous smooth-muscle homo genate: cGMP-inhibited PDE (PDE III), cAMP-specific PDE (PDE IV), and cGMP-specific PDE (PDE V). All PDE inhibitors tested showed a relaxati on effect on isolated human cavernous smooth-muscle, albeit with diffe ring potency. Quazinone (a selective PDE III inhibitor) had potency at least equal to that of papaverine (a non-selective PDE inhibitor) and had a superior effect as compared with Rolipram (a selective PDE IV i nhibitor) and zaprinast (a selective PDE V inhibitor). The present stu dy provides the rationale and opens the possibility of using selective PDE inhibitors in the treatment of patients with erectile dysfunction .