[Significance of phosphodiesterase isoenzymes in the control of human detrusor smooth muscle function. An immunohistochemical and functional study].
OBJECTIVE
The use of inhibitors of phosphodiesterase (PDE) isoenzymes 1 and 5 to treat overactive bladder has been suggested. To further evaluate the significance of PDE isoenzymes in detrusor smooth muscle relaxation, we investigated the effects of selective PDE inhibitors on the tension induced by carbachol of isolated human detrusor tissue. Using immunohistochemical methods, the expression of PDE1, PDE4, and PDE5 in human detrusor was also investigated.


METHODS
The expression of PDE1, PDE4, and PDE5 was evaluated by means of conventional immunohistochemistry (IHC). Using the organ bath technique, the effects of the PDE inhibitors vinpocetine, rolipram, sildenafil, tadalafil, and vardenafil on the tension induced by the muscarinic agonist carbachol (1 microM) were investigated.


RESULTS
The tension induced by carbachol was dose-dependently reversed by the PDE inhibitors; the maximum reversal of tension ranged from 7% (tadalafil) to 34% (vardenafil). IHC revealed that the expression of PDE isoenzymes was limited to the smooth musculature of the detrusor. While there was prominent expression of PDE4 and PDE5, immunoreactions indicating the presence of PDE1 were less abundant.


CONCLUSIONS
Despite the fact that inhibitors of PDE1, PDE4, and PDE5 exerted only a weak relaxant response on detrusor strips precontracted by carbachol, our findings indicate that both the cAMP and cGMP pathways might be involved in the relaxation mechanism of human detrusor smooth muscle.
Klinik für Urologie und Uro-Onkologie, Zentrum Chirurgie, Medizinische Hochschule Hochschule, Carl-Neuberg-Strasse 1, 30625 Hannover. sue_de_99@yahoo.de
S
S
Uckert
K
K
Sigl
E S
ES
Waldkirch
P
P
Sandner
E
E
Ulbrich
M
M
Oelke
C G
CG
Stief
M A
MA
Kuczyk
D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases