IDENTIFICATION OF DIFFERENT PHOSPHODIESTE RASE ISOENZYMES IN HUMAN DETRUSOR SMOOTH-MUSCLE

Phosphodiesterases (PDE) are a heterogeneous group of enzymes which hy drolyze the second messengers cyclic adenosine monophosphate (cAMP) an d cyclic guanosine monophosphate (cGMP). Therefore, PDE have a central role in the intracellular regulation of smooth muscle contractility. A characterization of PDE isoenzymes in the human detrusor smooth musc le was conducted for the first time and the effect of various PDE inhi bitors on carbachol contracted detrusor strips was investigated in vit ro. By addition of specific activitators and inhibitors of cAMP and cG MP hydrolysis, all known PDE isoenzyme families could be identified. W hile significant relaxations could only be induced by the nonspecific PDE inhibitor papaverine (relaxation 59.9 +/- 8.2%) and the PDE I inhi bitor vinpocetine (relaxation 51.4 +/- 7.9%), milrinone (PDE III inhib itor), rolipram (PDE IV inhibitor), zaprinast (PDE V/I inhibitor) and dipyridamole (PDE V inhibitor) were significantly less potent (relaxat ion <20%). Our results suggest an important functional role of calcium /calmodulin stimulated PDE I in the regulation of the human detrusor t one in vitro. The role of the PDE's II, III, IV and V is less dear, al though their minor effect may be explained by a possible intracellular compartimentation of these isoenzymes. further studies are needed to clarify whether regulation of the detrusor tone in humans is possible through selective modulation of the calcium/calmodulin stimulated PDE I.