title: Expression of cyclic AMP-dependent protein kinase isoforms in human cavernous arteries: functional significance and relation to phosphodiesterase type 4.
abstract: BACKGROUND
  The cyclic adenosine monophosphate-dependent protein kinase (cAK) is considered a key protein in the control of smooth muscle tone in the cardiovascular system. There is evidence that erectile dysfunction might be linked to systemic vascular disorders and arterial insufficiency, subsequently resulting in structural changes in the penile tissue. The expression and significance of cAK in human cavernous arteries (HCA) have not been evaluated.
  
  
  OBJECTIVE
  To evaluate the expression of cAK isoforms in HCA and examine the role of cAK in the cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated control of penile vascular smooth muscle.
  
  
  METHODS
  The expression and distribution of phosphodiesterase type 4 (PDE4) and cAK isoforms in sections of HCA were investigated by means of immunohistochemistry and Western blot analysis. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the relaxation of isolated preparations of HCA (diameter > 100 µm) induced by rolipram, sildenafil, tadalafil, and vardenafil were studied using the organ bath technique.
  
  
  METHODS
  Investigate the expression of cAK in relation to α-actin and PDE4 in HCA and evaluate the effects of an inhibition of cAK on the relaxation induced by inhibitors of PDE4 and PDE5 of isolated penile arteries.
  
  
  RESULTS
  Immunosignals specific for cAKIα, IIα, and IIβ were observed within the wall of HCA. Double stainings revealed colocalization of cAK with α-actin and PDE4. The expression of cAK isoforms was confirmed by Western blot analysis. The reversion of tension induced by inhibitors of PDE4 and PDE5 of isolated penile vascular tissue were attenuated significantly by Rp-8-CPT-cAMPS.
  
  
  CONCLUSIONS
  Our results demonstrate the expression of cAK isoforms in the smooth musculature of HCA and its colocalization with PDE4. A significant role for cAK in the regulation mediated by cAMP and cGMP of vascular smooth muscle tone in HCA can also be assumed.
authors.affiliation: Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany.
authors.forename: Eginhard S
authors.initials: ES
authors.lastname: Waldkirch
authors.affiliation: Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany. Electronic address: streetgang@gmx.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ückert
authors.affiliation: MorphoSys AG, Martinsried, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Sigl
authors.affiliation: Hannover Medical School-Department of Dermatology and Allergology, Hannover, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Satzger
authors.affiliation: Private Dermatological Practice, Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Geismar
authors.affiliation: Otto-von-Guericke-University, Faculty of Medicine-Institute for Biochemistry and Cell Biology, Magdeburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Langnäse
authors.affiliation: Otto-von-Guericke-University, Faculty of Medicine-Institute for Biochemistry and Cell Biology, Magdeburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Richter
authors.affiliation: Frankfurter Diakonie-Kliniken, St. Markus Academic Hospital-Department of Urology, Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: University Vita Salute, Faculty of Medicine, San Raffaele Hospital-Department of Urology, Urological Research Institute, Milan, Italy.
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000199:Actins / Q000502:physiology; D000328:Adult; D001158:Arteries / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000502:physiology*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010413:Penis / Q000098:blood supply*; D020033:Protein Isoforms / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D000199:Actins; D020033:Protein Isoforms; D017868:Cyclic AMP-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D000095043:Cyclin-Dependent Kinase-Activating Kinase