THE INFLUENCE OF VARIOUS PHOSPHODIESTERAS E INHIBITORS ON THE PORCINEDETRUSOR TONE IN-VITRO

The influence of various isoenzyme-specific phosphodiesterase (PDE) in hibitors on carbachol-induced porcine detrusor contractions were inves tigated in vitro and an isoenzyme separation from tissue homogenate pe rformed. Milrinone (PDE III inhibitor), rolipram (PDE IV inhibitor) an d zaprinast (PDE V inhibitor) had only minor relaxing effects (< 20%) at maximum concentrations while papaverine (nonselective PDE inhibitor ) and vinpocetine (PDE I inhibitor) were significantly more po tent (7 3 +/- 4.3% and 53 +/- 7.9%). All known PDE isoenzyme families except P DE III were detected in the 42,000 g supernatant of tile detrusor homo genate. Calcium/calmodulin-stimulatod PDE I may be of functional impor tance in the regulation of the lower urinary tract in the pig. The iso enzyme-selective modulation of intracellular key enzymes is a novel ap proach in the regulation of detrusor tone.