title: Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate.
abstract: OBJECTIVE
  Besides their role in contraction, α1-adrenoceptors may be involved in prostate hyperplasia. This would require receptor signaling by growth-promoting pathways. Akt (syn. Protein kinase B) is an important regulator of growth and differentiation.
  
  
  OBJECTIVE
  To investigate whether α1-adrenoceptors in the human prostate activate Akt.
  
  
  METHODS
  Prostate tissue was obtained from patients undergoing radical prostatectomy. Akt expression was investigated by RT-PCR, Western blot, and immunohistochemistry. Akt activation by noradrenaline (30 μM) and phenylephrine (10 μM) was assessed by Western blot analyses with a phospho-specific antibody. The effects of the Akt inhibitors FPA-124 and 10-DEBC on phenylephrine-, noradrenaline- and electric field stimulation- (EFS-) induced contraction were studied in myographic measurements.
  
  
  RESULTS
  mRNA of all three Akt isoforms (Akt1, Akt2, Akt3) was detected by RT-PCR in all prostate samples (n=6 patients). Protein expression was confirmed by Western blot analysis (n=8 patients). Immunohistochemical staining for Akt revealed strong immunoreactivity in prostate smooth muscle cells (n=5 patients). Stimulation of prostate tissues with noradrenaline (30 μM, n=8 patients) or phenylephrine (10 μM, n=7 patients) caused significant Akt phosphorylation at serine-473, indicating activation of Akt. FPA124 and 10-DEBC were without effects on noradrenaline-, phenylephrine-, or EFS-induced contraction of prostate strips.
  
  
  CONCLUSIONS
  Prostate α1-adrenoceptors activate Akt. Consequently, Akt is a target of α1-blocker therapy, which has been unknown to date. Our findings point to functions of prostate α1-adrenoceptors besides contraction.
authors.affiliation: Department of Urology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Strittmatter
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.forename: Alexander
authors.initials: A
authors.lastname: Roosen
authors.forename: Beata
authors.initials: B
authors.lastname: Rutz
authors.forename: Boris
authors.initials: B
authors.lastname: Schlenker
authors.forename: Sebastian
authors.initials: S
authors.lastname: Limmer
authors.forename: Raphaela
authors.initials: R
authors.lastname: Waidelich
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.forename: Martin
authors.initials: M
authors.lastname: Hennenberg
mesh_terms: D015153:Blotting, Western; D004576:Electromyography; D004789:Enzyme Activation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D051057:Proto-Oncogene Proteins c-akt; D009638:Norepinephrine