Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro

Urologia Internationalis
C G StiefU Jonas

Abstract

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 ...Continue Reading

Citations

Jan 1, 1997·World Journal of Urology·K E Andersson, C G Stief
Mar 16, 2011·Journal of Endourology·Abdulrahman Al-AownEvangelos Liatsikos
Nov 22, 2000·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·K ShimizuS Nakajyo
Oct 16, 2008·Der Urologe. Ausg. A·A J BeckerC G Stief
Aug 6, 2000·Japanese Journal of Pharmacology·K ShimizuS Nakajyo
Sep 8, 2001·The Journal of Urology·S Y NakadaR Saban
Apr 28, 2005·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Marcia A WheelerRobert M Weiss
May 15, 2007·Urologia Internationalis·A Erdem CandaOktay Nazli
May 10, 2013·Expert Review of Clinical Pharmacology·Stefan ÜckertMatthias Oelke
May 8, 1999·BJU International·T J JerdeS Y Nakada
May 16, 2021·Basic & Clinical Pharmacology & Toxicology·Iris LimRuss Chess-Williams

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