title: Phosphodiesterase type 2 distribution in the guinea pig urinary bladder.
abstract: BACKGROUND
  Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall.
  
  
  METHODS
  Six male guinea pig bladders were dissected and treated in 2 ml Krebs' solution and 10 µM of the specific PDE2 inhibitor, Bay 60-7550 at 36 °C for 30 min. After stimulating tissues with 100 µM of diethylamine-NONOate for 10 min, the tissues were snap frozen and cut in 10 µm sections which were examined for cGMP immune-reactivity, co-stained with either vimentin, synaptic vesicle protein 2, calcitonin gene-related protein and protein gene product 9.5.
  
  
  RESULTS
  PDE2 inhibitor Bay 60-7550 inhibits cGMP breakdown the most in the urothelial and suburothelial layers, as well as on the nerve fibres. After inhibition by Bay 60-7550, cGMP was mainly expressed in the intermuscle interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity.
  
  
  CONCLUSIONS
  Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.
authors.affiliation: Department of Urology, Maastricht University Medical Centre (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands. Sajjad_r@yahoo.com.|The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. Sajjad_r@yahoo.com.
authors.forename: M S
authors.initials: MS
authors.lastname: Rahnama'i
authors.affiliation: The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Hohnen
authors.affiliation: Department of Urology, Maastricht University Medical Centre (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands.|The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Ph E V
authors.initials: PE
authors.lastname: Van Kerrebroeck
authors.affiliation: Department of Urology, Maastricht University Medical Centre (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands.|The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: van Koeveringe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D001743:Urinary Bladder / Q000201:enzymology* / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000201:enzymology* / Q000473:pathology; D019459:Urothelium / Q000201:enzymology
chemical_list: D015415:Biomarkers; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2
keywords: Bladder; OAB; Overactive bladder syndrome; PDE2; Phosphodiesterase type 2; Urothelium