Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue
Article first published online: 27 SEP 2012
© 2012 BJU INTERNATIONAL
Volume 110, Issue 11c, pages E1196–E1201, December 2012
How to Cite
Kedia, G. T., Sonnenberg, J. E., Kuczyk, M. A. and Ückert, S. (2012), Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue. BJU International, 110: E1196–E1201. doi: 10.1111/j.1464-410X.2012.11529.x
- Issue published online: 21 DEC 2012
- Article first published online: 27 SEP 2012
- Accepted for publication 1 June 2012
- prostate smooth muscle;
- arginase enzymes;
- nitric oxide (NO);
- cyclic GMP
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.
- • 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.
MATERIALS AND 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.
- • 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.
- • 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.