Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. II. Effect of various PDE inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro.

Abstract

Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of smooth musculature. The 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 functional relevance of the cAMP versus the cGMP pathways in the regulation of the detrusor smooth muscle tone was assessed. Relaxant responses to various PDE inhibitors, forskolin and sodium nitroprusside (SNP) were investigated in vitro using a standard organ bath setup. Cyclic nucleotide levels were measured after incubation with the same substances using cAMP and cGMP radioimmunoassays (RIAs). Significant relaxant responses were only induced by non-selective PDE inhibition, the PDE I inhibitor vinpocetine and the adenylate cyclase activator forskolin. Relaxant 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 muscle tone in vitro.