title: Alpha1-adrenoceptor signaling in the human prostate involves regulation of p38 mitogen-activated protein kinase.
abstract: OBJECTIVE
  To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although α1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate α1-adrenoceptors is not sufficiently understood.
  
  
  METHODS
  Prostate tissue was obtained from patients undergoing radical prostatectomy. The effect of phenylephrine (10 μM) on p38 activity was assessed by Western blot analysis with a phospho-specific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 μM) on phenylephrine-induced contraction was studied in myographic measurements.
  
  
  RESULTS
  Stimulation of human prostate tissue with phenylephrine resulted in reduced threonine180/tyrosine182 phosphorylation of p38, indicating deactivation of p38 (P = .039 after 5 minutes). Immunohistochemical staining demonstrated expression of p38 in stromal cells of human prostate tissue. Immunofluorescence staining identified these cells as smooth muscle cells, as p38 colocalized with immunoreactivity for α-smooth muscle actin. The p38 inhibitor SB 202190 was without effect on phenylephrine-induced contraction.
  
  
  CONCLUSIONS
  Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate α1-adrenoceptors. In addition to mediating contraction, prostate α1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in α1-adrenergic contraction, and points to α1-adrenoceptor functions beyond contraction.
authors: Department of Urology, University of Munich, Munich, Germany.
authors: Frank
authors: F
authors: Strittmatter
authors: Christian
authors: C
authors: Gratzke
authors: Sebastian
authors: S
authors: Walther
authors: Johanna
authors: J
authors: Göttinger
authors: Christer
authors: C
authors: Beckmann
authors: Alexander
authors: A
authors: Roosen
authors: Boris
authors: B
authors: Schlenker
authors: Oliver
authors: O
authors: Reich
authors: Christian G
authors: CG
authors: Stief
authors: Martin
authors: M
authors: Hennenberg
mesh_terms: D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D009119:Muscle Contraction; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole