(210) EXPRESSION OF POTENTIAL FUNCTIONAL SIGNIFICANCE OF ARGINASE ISOENZYMES (L-ARGININE-AMINIDOHYDROLASES) IN THE HUMAN PROSTATE

There is evidence that the nitric oxide (NO)/cyclic GMP pathway contributes mainly to the control of the normal function of smooth musculature in the human prostate. The activity of nitric oxide synthases (NOS) is in part regulated by arginase enzymes (L-arginine-aminidohydrolases, Arg), known to hydrolyse the amino acid L-arginine (the common substrate of NOS and Arg) to L-ornithineand urea. We have investigated in the transition zone of the human prostate the expression and potential functional significance of arginase enzymes type I and type II (Arg I, Arg II).

Human prostate tissue was obtained from male subjects who had undergone pelvic surgery (prostatectomy/cystectomy). The expression of Arg I and Arg II was investigated by means of Western blot analysis. Using the tissue bath technique, the effects were assessed of the cumulative administration of arginase inhibitors (DFMO, H-Orn-OH^.HCl, H-Ile-OH, nor-NOHA, 1 nM - 10 μM each) on the tension induced by the alpha-adrenergic agonist norepinephrine (NE) of isolated prostate tissue. The production of cyclic GMP in the tissue strips in response to exposure to the compounds was measured also.

Western blot analysis revealed the expression of Arg I and Arg II in the transition zone of the prostate. The tension induced by NE was antagonized by the arginase inhibitors with the following rank order of efficacy: H-Orn-OH^.HCl ≥ H-Ile-OH ≥ DFMO > nor-NOHA (in a range from -13% to -25%). The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors was 4-fold to 14-fold.

Arg I and Arg II are expressed in 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 prostate smooth muscle induced by the activation of alpha-adrenoceptors and enhance the accumulation of cyclic GMP.

The authors have no conflicts of interest to declare.