title: Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate.
abstract: OBJECTIVE
  Experimental studies have provided the basis for the evaluation of inhibitors of the phosphodiesterase type 5 (PDE5) in the treatment of lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). It has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by their effects on the urinary bladder rather than on the prostate. Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification.
  
  
  METHODS
  The present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKIα, cGKIß), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP).
  
  
  RESULTS
  In the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα, and cGKIß, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP.
  
  
  CONCLUSIONS
  The findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. This might be of significance for the identification of new pharmacological avenues to treat patients with symptomatic BPH.
authors.affiliation: Division of Surgery, Department of Urology & Urological Oncology, Hannover Medical School, 30625, Hannover, Germany. streetgang@gmx.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Ückert
authors.forename: Eginhard S
authors.initials: ES
authors.lastname: Waldkirch
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelke
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000368:Aged; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP