title: Expression and distribution of phosphodiesterase isoenzymes in the human seminal vesicles.
abstract: BACKGROUND
  Phosphodiesterase (PDE) isoenzymes have been shown to play a role in the control of human male genital tissues. There are hints from basic research and clinical studies that PDE5 inhibitors may have the ability to retard the male ejaculatory response. While the expression of PDE isoenzymes in the human seminal vesicles (SVs) has been described, the distribution of cyclic adenosine monophosphate (AMP)- and cyclic guanosine monophosphate (GMP)-PDEs has not yet been investigated.
  
  
  OBJECTIVE
  The aim of this study was to elucidate the expression and distribution of PDE isoenzymes PDE3A, PDE4 (isoforms A and B), PDE5A, and PDE11A in human SV tissue.
  
  
  METHODS
  Using immunohistochemistry (double-labeling techniques, laser fluorescence microscopy), the occurrence of PDE3A, PDE4A, PDE4B, PDE5A, and PDE11A, the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and protein gene product 9.5 (PGP 9.5) was examined in sections of SV. Cytosolic supernatants prepared from isolated human SV tissue were subjected to Western blot analysis using specific anti-PDE antibodies.
  
  
  METHODS
  The expression and distribution by of PDE3A, PDE4A, PDE4B, PDE5A, and PDE11A in the human SV were investigated by means of immunohistochemistry and Western blot analysis.
  
  
  RESULTS
  Immunosignals specific for PDE3A were seen in both the smooth muscle and the glandular epithelium, whereas staining for PDE4A, PDE5A, and PDE11A was mainly limited to epithelial cells. Varicose nerve fibers transversing the sections also presented staining for PDE3A. In nerve fibers and nerve endings, PDE4A and PDE4B were found co-localized with VIP; PDE5A-positive nerves also presented immunosignals specific for CGRP. The expression of said PDE isoenzymes was confirmed by Western blotting.
  
  
  CONCLUSIONS
  The results indicate that cyclic AMP- and cyclic GMP-PDE isoenzymes are involved in the control of secretory activity and efferent neurotransmission in the SV. These findings might be of importance with regard to the identification of new therapeutic avenues to treat premature ejaculation.
authors.affiliation: Department of Urology and Urological Oncology, Hannover Medical School, Division of Surgery, Hannover, Germany. sue_de_99@yahoo.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Ückert
authors.forename: Eginhard S
authors.initials: ES
authors.lastname: Waldkirch
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Sonnenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Sandner
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D015153:Blotting, Western; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000201:enzymology*; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D010727:Phosphoric Diester Hydrolases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517287:PDE3A protein, human; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C406737:PDE11A protein, human; C517381:PDE5A protein, human