title: Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue.
abstract: What's known on the subject? and What does the study add? A previous study by Lexander et al. in 2005, using two-dimensional gel electrophoresis, demonstrated the expression of arginase type II in the different anatomical regions of the prostate; however, to date, no study has addressed, using an in vitro approach, the role of arginase isoenzymes in the human prostate. The results of the present study demonstrate that: both arginase isoenzymes, Arg I and Arg II, are expressed in the transition zone of the human prostate; the inhibition of arginase antagonized, to a certain degree, the tension brought about by noradrenaline in isolated human prostate tissue; exposure of human prostate tissue to arginase inhibitors enhanced the local production of cyclic GMP; and inhibition of arginase enzymes in the human prostate may augment the activity of the nitric oxide/cyclicGMP pathway.
  
  
  OBJECTIVE
  • To investigate the expression of arginase isoenzymes type I (Arg I) and type II (Arg II) in the transition zone of the human prostate and the functional significance of arginase enzymes in the control of prostate smooth muscle.
  
  
  METHODS
  • Human prostate tissue was obtained from male patients who had undergone pelvic surgery. • The expression of Arg I and Arg II was investigated using Western blot analysis. • Using the organ bath technique, the effects of cumulative administration of difluoromethylornithine (DFMO), H-Orn-OH × HCl, H-Ile-OH and N-ω-hydroxy-nor-L-arginine (nor-NOHA; 1 nM-10 µM) on the tension induced by noradrenaline in isolated prostate tissue were assessed. • Tissue strips were also exposed to arginase inhibitors and the production of cyclic GMP was determined.
  
  
  RESULTS
  • Western blot analysis showed the expression of Arg I and Arg II in the transition zone of the prostate. • The tension induced by noradrenaline was antagonized by the drugs in the following rank order of efficacy: H-Orn-OH × HCl ≥ H-Ile-OH ≥ DFMO > nor-NOHA; however, the maximum reversion of tension recorded ranged from only -25 to -13%. • The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors ranged from four- to 14-fold.
  
  
  CONCLUSIONS
  • Arg I and Arg II are expressed in the transition zone of the human prostate. • Isometric tension studies and measurement of cyclic GMP showed that inhibition of arginase can reverse, to a certain degree, the tension of human prostate tissue induced by the activation of α-adrenoceptors and enhance the accumulation of cyclic GMP. • Future studies should explore further the role of arginase enzymes in the relaxation mediated by nitric oxide in prostate smooth muscle.
authors.affiliation: Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany. kedia.george@mh-hannover.de
authors.forename: George T
authors.initials: GT
authors.lastname: Kedia
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Sonnenberg
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Stefan
authors.initials: S
authors.lastname: Uckert
mesh_terms: D000368:Aged; D001119:Arginase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015153:Blotting, Western; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D001119:Arginase; D000518:Eflornithine