CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN DETRUSOR SMOOTH-MUSCLE .2. EFFECT OF VARIOUS PDE INHIBITORS ON SMOOTH-MUSCLE TONE AND CYCLIC-NUCLEOTIDE LEVELS IN-VITRO

Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide met abolism and, thus, contraction and relaxation of smooth musculature. T he aim of the present study was to evaluate the functional effects of isoenzyme-selective inhibitors and their effects on cyclic nucleotide levels in the human detrusor smooth muscle. In addition, the functiona l relevance of the cAMP versus the cGMP pathways in the regulation of the detrusor smooth muscle tone was assessed. Relaxant responses to va rious PDE inhibitors, forskolin and sodium nitroprusside (SNP) were in vestigated in vitro using a standard organ bath setup. Cyclic nucleoti de levels were measured after incubation with the same substances usin g cAMP and cGMP radioimmunoassays (RIAs). Significant relaxant respons es were only induced by non-selective PDE inhibition, the PDE I inhibi tor vinpocetine and the adenylate cyclase activator forskolin. Relaxan t responses to these substances were paralleled by increases in cyclic nucleotide levels. Our data suggest that the cAMP pathway and calcium /calmodulin-stimulated PDE (PDE I) may be of functional importance in the regulation of the human detrusor smooth tone in vitro.