CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN DETRUSOR SMOOTH-MUSCLE .1. IDENTIFICATION AND CHARACTERIZATION

Phosphodiesterases (PDEs) are key enzymes involved in the regulation o f intracellular cyclic nucleotide metabolism. The aim of the present s tudy was to identify and to characterize the PDE isoenzymes present in the human detrusor smooth muscle. Human detrusor PDE isoenzymes were separated by Q-Sepharose anion exchange and calmodulin-agarose affinit y chromatography and characterized upon their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. All fiv e presently known PDE isoenzyme families were identified: one high-aff inity, low-K-m calcium/calmodulin-stimulated PDE I with a slight prefe rence for cGMP over cAMP, one cGMP-stimulated PDE II, one cGMP-inhibit ed PDE III, one cAMP-specific PDE IV and one cGMP-specific PDE IV. All five known PDE isoenzyme families exist in human detrusor smooth musc ulature. The kinetic characteristics, together with functional in vitr o studies, suggest that the PDE I may be of importance in the intracel lular regulation of the human detrusor smooth muscle tone.