CHARACTERIZATION OF PHOSPHODIESTERASE (PD E) ISOENZYMES IN THE HUMAN AND PORCINE DESTRUSOR MUSCULATURE

The effect of various isoenzyme-specific phosphodiesterase (PDE) inhib itors on carbachol induced porcine and human destrusor contractions we re investigated in vitro and an isolation and characterisation of PDE isoenzymes present in porcine and human detrusor homogenate was done. Milrinone (PDE III inhibitor), rolipram (PDE IV inhibitor), zaprinast (PDE V/I inhibitor) and dipyridamole (PDE V inhibitor, human tissue on ly) had only minor relaxant effects at maximum concentrations (< 20%) while papaverine (nonselective PDE inhibitor) and vinpocetine (PDE I i nhibitor) were significantly more potent (porcine detrusor: 73+/-4.3% and 53+/-7.9%, human detrusor: 59.9+/-8.2% and 51.4+/-7.9% relaxation) . One PDE I, one PDE II, two PDE IV and two PDE V were identified from the 42.000 g supernatant of the porcine detrusor homogenates. In the cytosolic fraction of the human tissue homogenate all five known PDE ( PDE I-V) were found. The calcium/calmodulin stimulated PDE I seems to be of functional importance in the regulation of the porcine as well a s the human detrusor tone. Despite distinct biochemical differences th e pig is a valuable in vitro model for the study of the intracellular regulation cascade of the detrusor smooth muscle. Isoenzyme-specific m odulation of intracellular key enzymes is a novel approach for detruso r tone regulation.